Large scale cultivation of genetically modified microalgae: A new era for environmental risk assessment

The genetic modification of microalgal strains for enhanced or modified metabolic activity shows great promise for biotechnological exploitation. However, of key concern for many is the safety of GM technology and GMOs with regard to both the environment and human health, and how these concerns are met will play a key role in ensuring how successful commercialisation of GM algae is achieved. Commercialisation opportunities for GM microalgae will inevitably require translation from laboratory to industrial settings, on scales beyond those typically associated with the current biotechnology sector. Here we provide an overview of the current situation with regards to GM techniques and legislation, and the implications of large-scale cultivation with regards to developing a safe and effective risk assessment system for contained and uncontained activities. We discuss the rationale and options for modification and the implications for risks associated with scale up to human health and the environment, current grey areas in political/technical legislation, the use of contained/uncontained production systems, deliberate release and monitoring strategies. We conclude that while existing procedures are not entirely sufficient for accurate and exhaustive risk assessment, there exists a substantial knowledge base and expertise within the existing aquaculture, fermentation and (algal) biotechnology industries that can be combined and applied to ensure safe use in the future

Photodissociation and the Morphology of HI in Galaxies

Young massive stars produce Far-UV photons which dissociate the molecular gas on the surfaces of their parent molecular clouds. Of the many dissociation products which result from this ``back-reaction'', atomic hydrogen \HI is one of the easiest to observe through its radio 21-cm hyperfine line emission. In this paper I first review the physics of this process and describe a simplified model which has been developed to permit an approximate computation of the column density of photodissociated \HI which appears on the surfaces of molecular clouds. I then review several features of the \HI morphology of galaxies on a variety of length scales and describe how photodissociation might account for some of these observations. Finally, I discuss several consequences which follow if this view of the origin of HI in galaxies continues to be successful.Comment: 18 pages, 7 figures in 8 files, invited review paper for the conference "Penetrating Bars Through Masks of Cosmic Dust: The Hubble Tuning Fork Strikes a New Note", South Africa, June 2004. Proceedings to be published by Kluwer, eds. D.L. Block, K.C. Freeman, I. Puerari, R. Groess, & E.K. Bloc

Potential for improved ATSR dual‐view SST retrieval

Recent validation studies have confirmed that the first along‐track scanning radiometer (ATSR) can retrieve sea surface temperature (SST) to an accuracy of 0.3K even in the presence of heavy atmospheric aerosol. However, using the standard (pre‐launch) retrieval, this accuracy is achieved only when data from all three thermal channels (3.7, 11 and 12 µm) are available; in the absence of 3.7 µm data, retrieved SSTs are subject to significant cold bias. As 3.7 µm data are useful only for nighttime observations, and ATSR's 3.7 µm channel failed in May 1992, only 11 and 12 µm data informed SST derivation for most of the 1991–1996 mission. We demonstrate the potential for improvement in this retrieval, based on comparison of observed brightness temperatures with precise SSTs derived using 3.7 µm data. A reduction in global‐mean cold bias from >0.6K to <0.1K is achieved, with standard deviation approximately halved. We also examine the treatment of optical pathlength variation around the ATSR swath

A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes

Peptides that are antigenic for T lymphocytes are ligands for two receptors, the class I or II glycoproteins that are encoded by genes in the major histocompatibility complex, and the idiotypic / chain T-cell antigen receptor1–9. That a peptide must bind to an MHC molecule to interact with a T-cell antigen receptor is the molecular basis of the MHC restriction of antigen-recognition by T lymphocytes10,11. In such a trimolecular interaction the amino-acid sequence of the peptide must specify the contact with both receptors: agretope residues bind to the MHC receptor and epitope residues bind to the T-cell antigen receptor12,13. From a compilation of known antigenic peptides, two algorithms have been proposed to predict antigenic sites in proteins. One algorithm uses linear motifs in the sequence14, whereas the other considers peptide conformation and predicts antigenicity for amphipathic -helices15,16. We report here that a systematic delimitation of an antigenic site precisely identifies a predicted pentapeptide motif as the minimal antigenic determinant presented by a class I MHC molecule and recognized by a cytolytic T lymphocyte clone

Towards an Achievable Performance for the Loop Nests

Numerous code optimization techniques, including loop nest optimizations, have been developed over the last four decades. Loop optimization techniques transform loop nests to improve the performance of the code on a target architecture, including exposing parallelism. Finding and evaluating an optimal, semantic-preserving sequence of transformations is a complex problem. The sequence is guided using heuristics and/or analytical models and there is no way of knowing how close it gets to optimal performance or if there is any headroom for improvement. This paper makes two contributions. First, it uses a comparative analysis of loop optimizations/transformations across multiple compilers to determine how much headroom may exist for each compiler. And second, it presents an approach to characterize the loop nests based on their hardware performance counter values and a Machine Learning approach that predicts which compiler will generate the fastest code for a loop nest. The prediction is made for both auto-vectorized, serial compilation and for auto-parallelization. The results show that the headroom for state-of-the-art compilers ranges from 1.10x to 1.42x for the serial code and from 1.30x to 1.71x for the auto-parallelized code. These results are based on the Machine Learning predictions.Comment: Accepted at the 31st International Workshop on Languages and Compilers for Parallel Computing (LCPC 2018

The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance

Expectation violation and attention to pain jointly modulate neural gain in somatosensory cortex

The neural processing and experience of pain are influenced by both expectations and attention. For example, the amplitude of event-related pain responses is enhanced by both novel and unexpected pain, and by moving the focus of attention towards a painful stimulus. Under predictive coding, this congruence can be explained by appeal to a precision-weighting mechanism, which mediates bottom-up and top-down attentional processes by modulating the influence of feedforward and feedback signals throughout the cortical hierarchy. The influence of expectation and attention on pain processing can be mapped onto changes in effective connectivity between or within specific neuronal populations, using a canonical microcircuit (CMC) model of hierarchical processing. We thus implemented a CMC within dynamic causal modelling for magnetoencephalography in human subjects, to investigate how expectation violation and attention to pain modulate intrinsic (within-source) and extrinsic (between-source) connectivity in the somatosensory hierarchy. This enabled us to establish whether both expectancy and attentional processes are mediated by a similar precision-encoding mechanism within a network of somatosensory, frontal and parietal sources. We found that both unexpected and attended pain modulated the gain of superficial pyramidal cells in primary and secondary somatosensory cortex. This modulation occurred in the context of increased lateralized recurrent connectivity between somatosensory and fronto-parietal sources, driven by unexpected painful occurrences. Finally, the strength of effective connectivity parameters in S1, S2 and IFG predicted individual differences in subjective pain modulation ratings. Our findings suggest that neuromodulatory gain control in the somatosensory hierarchy underlies the influence of both expectation violation and attention on cortical processing and pain perception

Identification of furfural resistant strains of Saccharomyces cerevisiae and Saccharomyces paradoxus from a collection of environmental and industrial isolates

Background Fermentation of bioethanol using lignocellulosic biomass as a raw material provides a sustainable alternative to current biofuel production methods by utilising waste food streams as raw material. Before lignocellulose can be fermented it requires physical, chemical and enzymatic treatment in order to release monosaccharides, a process that causes the chemical transformation of glucose and xylose into the cyclic aldehydes furfural and hydroxyfurfural. These furan compounds are potent inhibitors of Saccharomyces fermentation, and consequently furfural tolerant strains of Saccharomyces are required for lignocellulosic fermentation. Results This study investigated yeast tolerance to furfural and hydroxyfurfural using a collection of 71 environmental and industrial isolates of the baker’s yeast Saccharomyces cerevisiae and its closest relative Saccharomyces paradoxus. The Saccharomyces strains were initially screened for growth on media containing 100 mM glucose and 1.5 mg ml-1 furfural. Five strains were identified that showed a significant tolerance to growth in the presence of furfural and these were then screened for growth and ethanol production in the presence of increasing amounts (0.1-4 mg ml-1) of furfural. Conclusions Of the five furfural tolerant strains S. cerevisiae NCYC 3451 displayed the greatest furfural resistance, and was able to grow in the presence of up to 3.0 mg ml-1 furfural. Furthermore, ethanol production in this strain did not appear to be inhibited by furfural, with the highest ethanol yield observed at 3.0 mg ml-1 furfural. Although furfural resistance was not found to be a trait specific to any one particular lineage or population, three of the strains were isolated from environments where they might be continually exposed to low levels of furfural through the on-going natural degradation of lignocelluloses, and would therefore develop elevated levels of resistance to these furan compounds. Thus these strains represent good candidates for future studies of genetic variation relevant to understanding and manipulating furfural resistance and in the development of tolerant ethanologenic yeast strains for use in bioethanol production from lignocellulose processing

Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling