Structural,compositional and mineralogical characterization of carbonatitic copper sulfide: Run of mine,concentrate and tailings

The aim of this study was to determine the structural, compositional, and mineralogical composition of carbonatitic copper sulfide concentrator plant streams. Three samples, each from a different stream(run of mine(ROM), concentrate, and tailings) of a copper concentrator were characterized using various techniques, including stereomicroscopy, X-ray fluorescence, X-ray diffraction, Fourier transform infrared(FTIR) spectroscopy, scanning electron microscopy(SEM) in conjunction with energy-dispersive X-ray spectroscopy(EDS), and optical microscopy. The results reveal that each stream possesses its own unique compositional features. Carbonate minerals associated with calcite and dolomite, followed by quartz, remain the major minerals in both the ROM and tails streams. In the ROM stream, chalcopyrite appears to occur as veins within the carbonatite-hosting ore body. Mineral phase mutation was discovered in the tails stream because magnetite formerly identified in the ROM as the primary iron oxide had evolved into hematite. This metamorphosis was likely promoted by the concentration process. The concentration process was effective, upgrading the chalcopyrite content from 2 wt% in the ROM stream to 58 wt% in the concentrate stream; it was accompanied by bornite(4 wt%), anilite(3 wt%), and digenite(2.5 wt%). In addition, the concentrate stream exhibited properties distinctive from those of the other streams. The FTIR analysis showed the existence of a sulfide group related to the chalcopyrite mineral. Free chalcopyrite grains were observed in the concentrate by SEM analysis, and their mineral presence was supported by the EDS analysis results. All characterization techniques corresponded well with each other regarding the structure, chemistry, and composition of the samples.     

<Emphasis Type="Italic">Dictyostelium</Emphasis> dynamin B modulates cytoskeletal structures and membranous organelles

Dictyostelium discoideum cells produce five dynamin family proteins. Here, we show that dynamin B is the only member of this group of proteins that is initially produced as a preprotein and requires processing by mitochondrial proteases for formation of the mature protein. Our results show that dynamin B-depletion affects many aspects of cell motility, cell-cell and cell-surface adhesion, resistance to osmotic shock, and fatty acid metabolism. The mature form of dynamin B mediates a wide range and unique combination of functions. Dynamin B affects events at the plasma membrane, peroxisomes, the contractile vacuole system, components of the actin-based cytoskeleton, and cell adhesion sites. The modulating effect of dynamin B on the activity of the contractile vacuole system is unique for the Dictyostelium system. Other functions displayed by dynamin B are commonly associated with either classical dynamins or dynamin-related proteins.     

Matrix control of scarring

Repair of wounds usually results in restoration of organ function, even if suboptimal. However, in a minority of situations, the healing process leads to significant scarring that hampers homeostasis and leaves the tissue compromised. This scar is characterized by an excess of matrix deposition that remains poorly organized and weakened. While we know much of the early stages of the repair process, the transition to wound resolution that limits scar formation is poorly understood. This is particularly true of the inducers of scar formation. Here, we present a hypothesis that it is the matrix itself that is a primary driver of scar, rather than being simply the result of other cellular dysregulations.     

Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes

Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy.     

Stimulation of olfactory ensheathing cell motility enhances olfactory axon growth

Axons of primary olfactory neurons are intimately associated with olfactory ensheathing cells (OECs) from the olfactory epithelium until the final targeting of axons within the olfactory bulb. However, little is understood about the nature and role of interactions between OECs and axons during development of the olfactory nerve pathway. We have used high resolution time-lapse microscopy to examine the growth and interactions of olfactory axons and OECs in vitro. Transgenic mice expressing fluorescent reporters in primary olfactory axons (OMP-ZsGreen) and ensheathing cells (S100ß-DsRed) enabled us to selectively analyse these cell types in explants of olfactory epithelium. We reveal here that rather than providing only a permissive substrate for axon growth, OECs play an active role in modulating the growth of pioneer olfactory axons. We show that the interactions between OECs and axons were dependent on lamellipodial waves on the shaft of OEC processes. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons, whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity.     

Different roles of the human Orc6 protein in the replication initiation process

In eukaryotes, binding of the six-subunit origin recognition complex (ORC) to DNA provides an interactive platform for the sequential assembly of pre-replicative complexes. This process licenses replication origins competent for the subsequent initiation step. Here, we analyze the contribution of human Orc6, the smallest subunit of ORC, to DNA binding and pre-replicative complex formation. We show that Orc6 not only interacts with Orc1–Orc5 but also with the initiation factor Cdc6. Biochemical and imaging experiments reveal that this interaction is required for licensing DNA replication competent. Furthermore, we demonstrate that Orc6 contributes to the interaction of ORC with the chaperone protein HMGA1a (high mobility group protein A1a). Binding of human ORC to replication origins is not specified at the level of DNA sequence and the functional organization of origins is poorly understood. We have identified HMGA1a as one factor that might direct ORC to AT-rich heterochromatic regions. The systematic analysis of the interaction between ORC and HMGA1a revealed that Orc6 interacts with the acidic C-terminus of HMGA1a and also with its AT-hooks. Both domains support autonomous replication if targeted to DNA templates. As such, Orc6 functions at different stages of the replication initiation process. Orc6 can interact with ORC chaperone proteins such as HMGA1a to facilitate chromatin binding of ORC and is also an essential factor for pre-RC formation.     

Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm

The parathyroid hormone (PTH) receptor type 1 (PTHR), a G protein-coupled receptor (GPCR), transmits signals to two hormone systems—PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine—to regulate different biological processes. PTHR responds to these hormonal stimuli by activating heterotrimeric G proteins, such as G_S that stimulates cAMP production. It was thought that the PTHR, as for all other GPCRs, is only active and signals through G proteins on the cell membrane, and internalizes into a cell to be desensitized and eventually degraded or recycled. Recent studies with cultured cell and animal models reveal a new pathway that involves sustained cAMP signaling from intracellular domains. Not only do these studies challenge the paradigm that cAMP production triggered by activated GPCRs originates exclusively at the cell membrane but they also advance a comprehensive model to account for the functional differences between PTH and PTHrP acting through the same receptor.     

Protecting the boundary: the sentinel role of host defense peptides in the skin

The skin is our primary shield against microbial pathogens and has evolved innate and adaptive strategies to enhance immunity in response to injury or microbial insult. The study of antimicrobial peptide (AMP) production in mammalian skin has revealed several of the elegant strategies that AMPs use to prevent infection. AMPs are inducible by both infection and injury and protect the host by directly killing pathogens and/or acting as multifunctional effector molecules that trigger cellular responses to aid in the anti-infective and repair response. Depending on the specific AMP, these molecules can influence cytokine production, cell migration, cell proliferation, differentiation, angiogenesis and wound healing. Abnormal production of AMPs has been associated with the pathogenesis of several cutaneous diseases and plays a role in determining a patient’s susceptibility to pathogens. This review will discuss current research on the regulation and function of AMPs in the skin and in skin disorders.     

Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches

Naturally occurring antimicrobial peptides (AMPs) present several drawbacks that strongly limit their development into therapeutically valuable antibiotics. These include susceptibility to protease degradation and high costs of manufacture. To overcome these problems, researchers have tried to develop mimics or peptidomimetics endowed with better properties, while retaining the basic features of membrane-active natural AMPs such as cationic charge and amphipathic design. Protein epitope mimetics, multimeric (dendrimeric) peptides, oligoacyllysines, ceragenins, synthetic lipidated peptides, peptoids and other foldamers are some of the routes explored so far. The synthetic approach has led to compounds that have already entered clinical evaluation for the treatment of specific conditions, such as Staphylococcus (MRSA) infections. Should these trials be successful, an important proof-of-concept would be established, showing that synthetic oligomers rather than naturally occurring molecules could bring peptide-based antibiotics to clinical practice and the drug market for local and systemic treatment of medical conditions associated with multi-drug resistant pathogens.