New and Notable This Week

This week’s selection of recently published papers from MDPI journals.


The Oligomycin-Sensitivity Conferring Protein of Mitochondrial ATP Synthase: Emerging New Roles in Mitochondrial Pathophysiology

AbstractThe oligomycin-sensitivity conferring protein (OSCP) of the mitochondrial FOF1 ATP synthase has long been recognized to be essential for the coupling of proton transport to ATP synthesis. Located on top of the catalytic F1 sector, it makes stable contacts with both F1 and the peripheral stalk, ensuring the structural and functional coupling between FO and F1, which is disrupted by the antibiotic, oligomycin. Recent data have established that OSCP is the binding target of cyclophilin (CyP) D, a well-characterized inducer of the mitochondrial permeability transition pore (PTP), whose opening can precipitate cell death. CyPD binding affects ATP synthase activity, and most importantly, it decreases the threshold matrix Ca2+ required for PTP opening, in striking analogy with benzodiazepine 423, an apoptosis-inducing agent that also binds OSCP. These findings are consistent with the demonstration that dimers of ATP synthase generate Ca2+-dependent currents with features indistinguishable from those of the PTP and suggest that ATP synthase is directly involved in PTP formation, although the underlying mechanism remains to be established. In this scenario, OSCP appears to play a fundamental role, sensing the signal(s) that switches the enzyme of life in a channel able to precipitate cell death.


For Open Access Article, see: Antoniel, M.; Giorgio, V.; Fogolari, F.; Glick, G.D.; Bernardi, P.; Lippe, G. The Oligomycin-Sensitivity Conferring Protein of Mitochondrial ATP Synthase: Emerging New Roles in Mitochondrial PathophysiologyInt. J. Mol. Sci. 201415, 7513-7536.



Vegetation in Bangalore’s Slums: Boosting Livelihoods, Well-Being and Social Capital

Abstract: Urban greenery provides ecosystem services that play an important role in the challenging context of urban deprivation and poverty. This study assesses the social importance of vegetation through empirical assessment of 44 urban slums in the rapidly developing southern city of Bangalore, India. Vegetation played a major role in supporting nutrition by its role in food consumption, and in promoting health through the planting of species with medicinal use. Trees in slums also formed nodes for social activities including conversing and playing, domestic activities such as cooking and washing dishes, and livelihood activities such as the manufacture of broomsticks and tyre repair. Innovative methods of gardening were widely adopted, with kitchen gardens found planted in plastic bags, paint cans, old kitchen utensils and buckets, indicating the importance given to planting in environments with limited finances. Short and narrow trunked trees with medium-sized canopies and high economic value, such as Pongamia, were preferred. A greater focus on greening in slums is needed, and can provide an invaluable, inexpensive and sustainable approach to improve lives in these congested, deprived environments.


For Open Access Article, see: Gopal, D.; Nagendra, H. Vegetation in Bangalore’s Slums: Boosting Livelihoods, Well-Being and Social CapitalSustainability 20146, 2459-2473.


Indian Hedgehog in Synovial Fluid Is a Novel Marker for Early Cartilage Lesions in Human Knee Joint

Abstract: To determine whether there is a correlation between the concentration of Indian hedgehog (Ihh) in synovial fluid (SF) and the severity of cartilage damage in the human knee joints, the knee cartilages from patients were classified using the Outer-bridge scoring system and graded using the Modified Mankin score. Expression of Ihh in cartilage and SF samples were analyzed with immunohistochemistry (IHC), western blot, and enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected and compared Ihh protein levels in rat and mice cartilages between normal control and surgery-induced osteoarthritis (OA) group by IHC and fluorescence molecular tomography in vivo respectively. Ihh expression was increased 5.2-fold in OA cartilage, 3.1-fold in relative normal OA cartilage, and 1.71-fold in OA SF compared to normal control samples. The concentrations of Ihh in cartilage and SF samples was significantly increased in early-stage OA samples when compared to normal samples (r = 0.556; p < 0.001); however, there were no significant differences between normal samples and late-stage OA samples. Up-regulation of Ihh protein was also an early event in the surgery-induced OA models. Increased Ihh is associated with the severity of OA cartilage damage. Elevated Ihh content in human knee joint synovial fluid correlates with early cartilage lesions.


For Open Access Article, see: Zhang, C.; Wei, X.; Chen, C.; Cao, K.; Li, Y.; Jiao, Q.; Ding, J.; Zhou, J.; Fleming, B.C.; Chen, Q.; Shang, X.; Wei, L. Indian Hedgehog in Synovial Fluid Is a Novel Marker for Early Cartilage Lesions in Human Knee JointInt. J. Mol. Sci. 201415, 7250-7265.


HIV-1 Latency in Monocytes/Macrophages

Abstract: Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART) has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.


For Open Access Article, see: Kumar, A.; Abbas, W.; Herbein, G. HIV-1 Latency in Monocytes/MacrophagesViruses 20146, 1837-1860.


Mechanisms of Activation of Receptor Tyrosine Kinases: Monomers or Dimers

Abstract: Receptor tyrosine kinases (RTKs) play essential roles in cellular processes, including metabolism, cell-cycle control, survival, proliferation, motility and differentiation. RTKs are all synthesized as single-pass transmembrane proteins and bind polypeptide ligands, mainly growth factors. It has long been thought that all RTKs, except for the insulin receptor (IR) family, are activated by ligand-induced dimerization of the receptors. An increasing number of diverse studies, however, indicate that RTKs, previously thought to exist as monomers, are present as pre-formed, yet inactive, dimers prior to ligand binding. The non-covalently associated dimeric structures are reminiscent of those of the IR family, which has a disulfide-linked dimeric structure. Furthermore, recent progress in structural studies has provided insight into the underpinnings of conformational changes during the activation of RTKs. In this review, I discuss two mutually exclusive models for the mechanisms of activation of the epidermal growth factor receptor, the neurotrophin receptor and IR families, based on these new insights.


For Open Access Article, see: Maruyama, I.N. Mechanisms of Activation of Receptor Tyrosine Kinases: Monomers or DimersCells 20143, 304-330.



Co-Cultivation—A Powerful Emerging Tool for Enhancing the Chemical Diversity of Microorganisms

Abstract: Marine-derived bacteria and fungi are promising sources of novel bioactive compounds that are important for drug discovery programs. However, as encountered in terrestrial microorganisms there is a high rate of redundancy that results in the frequent re-discovery of known compounds. Apparently only a part of the biosynthetic genes that are harbored by fungi and bacteria are transcribed under routine laboratory conditions which involve cultivation of axenic microbial strains. Many biosynthetic genes remain silent and are not expressed in vitro thereby seriously limiting the chemical diversity of microbial compounds that can be obtained through fermentation. In contrast to this, co-cultivation (also called mixed fermentation) of two or more different microorganisms tries to mimic the ecological situation where microorganisms always co-exist within complex microbial communities. The competition or antagonism experienced during co-cultivation is shown to lead to a significantly enhanced production of constitutively present compounds and/or to an accumulation of cryptic compounds that are not detected in axenic cultures of the producing strain. This review highlights the power of co-cultivation for increasing the chemical diversity of bacteria and fungi drawing on published studies from the marine and from the terrestrial habitat alike.


For Open Access article, see: Marmann, A.; Aly, A.H.; Lin, W.; Wang, B.; Proksch, P. Co-Cultivation—A Powerful Emerging Tool for Enhancing the Chemical Diversity of MicroorganismsMar. Drugs 201412, 1043-1065.