Legionella pneumophila down-regulates MHC class I expression of human monocytic host cells and thereby inhibits T cell activation

Legionella (L.) pneumophila, the causative agent of Legionnaires disease, is an intracellular pathogen of alveolar macrophages that resides in a compartment displaying features of endoplasmatic reticulum (ER). In this study, we show that intracellular multiplication of L. pneumophila results in a remarkable decrease in MHC class I expression by the infected monocytes. During intracellular multiplication, L. pneumophila absorbs ER-resident chaperons such as calnexin and BiP, molecules that are required for the correct formation of the MHC class I complex. Due to reduced MHC class I expression, stimulation of allogeneic blood mononuclear cells was severely inhibited by infected host cells but cytotoxicity of autologous natural killer cells against Legionella-infected monocytes was not enhanced. Thus, reduced expression of MHC class I in infected monocytes may resemble a new immune escape mechanism induced by L. pneumophila.Received 22 November 2004; received after revision 27 December 2004; accepted 5 January 2005     

Cultural-Biology: Systemic Consequences of <Emphasis Type="Italic">Our</Emphasis> Evolutionary Natural Drift as Molecular Autopoietic Systems

Our purpose in this essay is to introduce new concepts (dynamic architecture and dynamic ecological organism-niche unity, among other) in a wide and recursive view of the systemic consequences of the following biological facts that I (Maturana in Biology of cognition, 1970, Unity and diversity of man. Le Seuil, Paris, 1978; Maturana and Varela in Autopoiesis and cognition: the realization of the living. D. Riedel Publishing Co, Boston, 1980, El Árbol del Conocimiento: Las Bases Biológicas del Conocer Humano, 1a Edición. Editorial Universitaria, Santiago, 1984; Maturana and Mpodozis in Rev Chil Hist Nat 73:261–310, 2000) and we (Maturana and Dávila in Habitar humano: en seis ensayos de biología-cultural. Juan Carlos Sáez Editorial, Chile, 2008) have presented that can be resumed as: (1) that as living systems we human beings are molecular autopoietic system; (2) that living systems live only as long as they find themselves in a medium that provides them with all the conditions that make the realization of their living possible, that is, in the continuous conservation of their relation of adaptation to the circumstances in which they find themselves; (3) that as a living system exists only in a relation of adaptation with the medium that operates as its ecological niche, its reproduction necessarily occurs as a process of systemic duplication or multiplication of the ecological organism-niche unity that it integrates; (4) that the worlds of doings that we generate as languaging beings in our conversations, explanations, reflections and theories are part of our ecological niche; and (5) that we human beings as living beings that exist in languaging, are biological–cultural beings in which our cultural and our biological manners of existences can be distinguished but cannot be separated. Of the systemic consequences of these biological facts that we consider in this essay, we wish to mention two as the principal: (1) that the diversification of manners of living produced in biological evolution is the result of differential survival in a changing medium through the conservation of adaptation, and not through competitive survival of the best; and (2) that we in our living as languaging human beings (observers) are the epistemological fundament of all that we do and know as such.     

Revealing the Face of Isis

This reply to Gash’s (Found Sci 2014) commentary on Nescolarde-Selva and Usó-Doménech (Found Sci 2014b) answers the questions raised and at the same time opens up new questions.     

Diagnosis of Organizational Soft Problems in a Peruvian Financial Institution by Systemic Thinking

Managing financial institutions in an underdeveloped economic context has become a real challenge nowadays. In order to reach the organization’s planned goals, they have to deal with structural, behavioral and informational problems. From the systemic point of view, this situation gets even worse when the company does not present organizational boundaries and a cohesive identification for their stakeholders. Thus, European countries have some special financial lines in order to help the development of micro credit in Latin communities in an attempt to help the local economy. However, institutions like Caixa dos Andes in Peru present management problems when dealing with this complexity. Based on this, how can the systemic eye help in the diagnosis of soft problems of a Peruvian financial company? This study aims to diagnose soft problems of a Peruvian financial company based on soft variables like identity, communication and autonomy and also intends to identify possible ways to redesign its basic framework. The (VSM––Viable System Model) method from Beer (1967), applied in this diagnostic study, was used in a practical way as a management tool for organizations’ analysis and planning. By describing the VSM’s five systems, the creation of a systemic vision or a total vision is possible, showing the organization’s complexity from the inside. Some company’s soft problems like double control, inefficient use of physical and human resources, low information flows, slowness, etc. The VSM presented an organizational diagnosis indicating effective solutions that do integrate its five systems.     

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.     

Visualizing heavy fermions emerging in a quantum critical Kondo lattice

In solids containing elements with f orbitals, the interaction between f-electron spins and those of itinerant electrons leads to the development of low-energy fermionic excitations with a heavy effective mass. These excitations are fundamental to the appearance of unconventional superconductivity and non-Fermi-liquid behaviour observed in actinide- and lanthanide-based compounds. Here we use spectroscopic mapping with the scanning tunnelling microscope to detect the emergence of heavy excitations with lowering of temperature in a prototypical family of cerium-based heavy-fermion compounds. We demonstrate the sensitivity of the tunnelling process to the composite nature of these heavy quasiparticles, which arises from quantum entanglement of itinerant conduction and f electrons. Scattering and interference of the composite quasiparticles is used to resolve their energy-momentum structure and to extract their mass enhancement, which develops with decreasing temperature. The lifetime of the emergent heavy quasiparticles reveals signatures of enhanced scattering and their spectral lineshape shows evidence of energy-temperature scaling. These findings demonstrate that proximity to a quantum critical point results in critical damping of the emergent heavy excitation of our Kondo lattice system.     

Optical nano-imaging of gate-tunable graphene plasmons

The ability to manipulate optical fields and the energy flow of light is central to modern information and communication technologies, as well as quantum information processing schemes. However, because photons do not possess charge, a way of controlling them efficiently by electrical means has so far proved elusive. A promising way to achieve electric control of light could be through plasmon polaritons—coupled excitations of photons and charge carriers—in graphene. In this two-dimensional sheet of carbon atoms, it is expected that plasmon polaritons and their associated optical fields can readily be tuned electrically by varying the graphene carrier density. Although evidence of optical graphene plasmon resonances has recently been obtained spectroscopically, no experiments so far have directly resolved propagating plasmons in real space. Here we launch and detect propagating optical plasmons in tapered graphene nanostructures using near-field scattering microscopy with infrared excitation light. We provide real-space images of plasmon fields, and find that the extracted plasmon wavelength is very short—more than 40 times smaller than the wavelength of illumination. We exploit this strong optical field confinement to turn a graphene nanostructure into a tunable resonant plasmonic cavity with extremely small mode volume. The cavity resonance is controlled in situ by gating the graphene, and in particular, complete switching on and off of the plasmon modes is demonstrated, thus paving the way towards graphene-based optical transistors. This successful alliance between nanoelectronics and nano-optics enables the development of active subwavelength-scale optics and a plethora of nano-optoelectronic devices and functionalities, such as tunable metamaterials, nanoscale optical processing, and strongly enhanced light–matter interactions for quantum devices and biosensing applications.