The Problem of Functional Boundaries in Prebiotic and Inter-Biological Systems

International audienceThe concept of organisational closure, interpreted as a set of internally produced and mutually dependent constraints, allows understanding organisms as functionally integrated systems capable of self-production and self-maintenance through the control exerted upon biosynthetic processes and the exchanges of matter and energy with the environment. One of the current challenges faced by this theoretical framework is to account for limit cases in which a robust functional closure cannot be realised from within. In order to achieve functional sufficiency and persist, prebiotic or biological systems may need to recruit external constraints or expand their network of control interactions to include other autonomous systems. These phenomena seem to contrast with the very idea of closure and the capability of living systems to specify their functional boundaries from within. This paper will analyse from an organisational perspective the role of environmental scaffolds and of different classes of intersystem interactions in prebiotic and su-pra-organismal biological scenarios, and show how the theoretical framework based on the notion of closure can account for these cases

Live Poultry Exposures, Hong Kong and Hanoi, 2006

Since 1997, the largest epidemic of highly pathogenic avian influenza (H5N1) ever recorded has caused 172 human and several billion bird deaths. Recently administered questionnaires determined that live poultry exposures have declined by ≈63% in Hong Kong since 2004 and that, in Vietnam, domestic backyard exposures to poultry are likely more important than retail exposures

The problem of functional boundaries in prebiotic and inter-biological systems

The concept of organisational closure, interpreted as a set of internally pro-duced and mutually dependent constraints, allows understanding organisms as functionally integrated systems capable of self-production and self-maintenance through the control exerted upon biosynthetic processes and the exchanges of matter and energy with the environment. One of the current challenges faced by this theoretical framework is to account for limit cases in which a robust functional closure cannot be realised from within. In order to achieve functional sufficiency and persist, prebiotic or biological systems may need to recruit external constraints or expand their network of control in-teractions to include other autonomous systems. These phenomena seem to contrast with the very idea of closure and the capability of living systems to specify their functional boundaries from within. This paper will analyse from an organisational perspective the role of environmental scaffolds and of dif-ferent classes of intersystem interactions in prebiotic and supra-organismal biological scenarios, and show how the theoretical framework based on the notion of closure can account for these cases

Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial

Background Inappropriate antibiotic use for acute respiratory tract infections is common in primary health care, but distinguishing serious from self-limiting infections is diffi cult, particularly in low-resource settings. We assessed whether C-reactive protein point-of-care testing can safely reduce antibiotic use in patients with non-severe acute respiratory tract infections in Vietnam. Method We did a multicentre open-label randomised controlled trial in ten primary health-care centres in northern Vietnam. Patients aged 1–65 years with at least one focal and one systemic symptom of acute respiratory tract infection were assigned 1:1 to receive either C-reactive protein point-of-care testing or routine care, following which antibiotic prescribing decisions were made. Patients with severe acute respiratory tract infection were excluded. Enrolled patients were reassessed on day 3, 4, or 5, and on day 14 a structured telephone interview was done blind to the intervention. Randomised assignments were concealed from prescribers and patients but not masked as the test result was used to assist treatment decisions. The primary outcome was antibiotic use within 14 days of follow-up. All analyses were prespecifi ed in the protocol and the statistical analysis plan. All analyses were done on the intention-totreat population and the analysis of the primary endpoint was repeated in the per-protocol population. This trial is registered under number NCT01918579. Findings Between March 17, 2014, and July 3, 2015, 2037 patients (1028 children and 1009 adults) were enrolled and randomised. One adult patient withdrew immediately after randomisation. 1017 patients were assigned to receive C-reactive protein point-of-care testing, and 1019 patients were assigned to receive routine care. 115 patients in the C-reactive protein point-of-care group and 72 patients in the routine care group were excluded in the intention-to-treat analysis due to missing primary endpoint. The number of patients who used antibiotics within 14 days was 581 (64%) of 902 patients in the C-reactive protein group versus 738 (78%) of 947 patients in the control group (odds ratio [OR] 0·49, 95% CI 0·40–0·61; p<0·0001). Highly signifi cant diff erences were seen in both children and adults, with substantial heterogeneity of the intervention eff ect across the 10 sites (I²=84%, 95% CI 66–96). 140 patients in the C-reactive protein group and 137 patients in the routine care group missed the urine test on day 3, 4, or 5. Antibiotic activity in urine on day 3, 4, or 5 was found in 267 (30%) of 877 patients in the C-reactive protein group versus 314 (36%) of 882 patients in the routine treatment group (OR 0·78, 95% CI 0·63–0·95; p=0·015). Time to resolution of symptoms was similar in both groups. Adverse events were rare, with no deaths and a total of 14 hospital admissions (six in the C-reactive protein group and eight in the control group). Interpretation C-reactive protein point-of-care testing reduced antibiotic use for non-severe acute respiratory tract infection without compromising patients’ recovery in primary health care in Vietnam. Health-care providers might have become familiar with the clinical picture of low C-reactive protein, leading to reduction in antibiotic prescribing in both groups, but this would have led to a reduction in observed eff ect, rather than overestimation. Qualitative analysis is needed to address diff erences in context in order to implement this strategy to improve rational antibiotic use for patients with acute respiratory infection in low-income and middle-income countries

Fabrication and characterization of linear diffusers based on concave micro lens arrays

Abstract: We present a new approach of beam homogenizing elements based on a statistical array of concave cylindrical microlens arrays. Those elements are used to diffuse light in only one direction and can be employed together with fly’s eye condensers to generate a uniform flat top line for high power coherent light sources. Conception, fabrication and characterization for such 1D diffusers are presented in this paper

Robustness and autonomy in biological systems: how regulatory mechanisms enable functional integration, complexity and minimal cognition through the action of second-order control constraints

Living systems employ several mechanisms and behaviors to achieve robustness and maintain themselves under changing internal and external conditions. Regulation stands out from them as a specific form of higher-order control, exerted over the basic regime responsible for the production and maintenance of the organism, and provides the system with the capacity to act on its own constitutive dynamics. It consists in the capability to selectively shift between different available regimes of self-production and self-maintenance in response to specific signals and perturbations, due to the action of a dedicated subsystem which is operationally distinct from the regulated ones. The role of regulation, however, is not exhausted by its contribution to maintain a living system’s viability. While enhancing robustness, regulatory mechanisms play a fundamental role in the realization of an autonomous biological organization. Specifically, they are at the basis of the remarkable integration of biological systems, insofar as they coordinate and modulate the activity of distinct functional subsystems. Moreover, by implementing complex and hierarchically organized control architectures, they allow for an increase in structural and organizational complexity while minimizing fragility. Finally, they endow living systems, from their most basic unicellular instances, with the capability to control their own internal dynamics to adaptively respond to specific features of their interaction with the environment, thus providing the basis for the emergence of minimal forms of cognition

Interfacing low-energy SAW nebulization with liquid chromatography-mass spectrometry for the analysis of biological samples

Soft ionization methods for the introduction of labile biomolecules into a mass spectrometer are of fundamental importance to biomolecular analysis. Previously, electrospray ionization (ESI) and matrix assisted laser desorption-ionization (MALDI) have been the main ionization methods used. Surface acoustic wave nebulization (SAWN) is a new technique that has been demonstrated to deposit less energy into ions upon ion formation and transfer for detection than other methods for sample introduction into a mass spectrometer (MS). Here we report the optimization and use of SAWN as a nebulization technique for the introduction of samples from a low flow of liquid, and the interfacing of SAWN with liquid chromatographic separation (LC) for the analysis of a protein digest. This demonstrates that SAWN can be a viable, low-energy alternative to ESI for the LC-MS analysis of proteomic samples

A Triad of Lys12, Lys41, Arg78 Spatial Domain, a Novel Identified Heparin Binding Site on Tat Protein, Facilitates Tat-Driven Cell Adhesion

Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs) have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat–heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR) spatial domain. This domain was also found to facilitate Tat-driven β1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events