T cell growth factor receptors. Quantitation, specificity, and biological relevance

To examine directly the hypothesis that T cell growth factor (TCGF) interacts with target cells in a fashion similar to polypeptide hormones, the binding of radiolabeled TCGF to various cell populations was investigated. The results indicate that TCGF interacts with activated T cells via a receptor through which it initiates the T cell proliferative response. Internally radiolabeled TCGF, prepared from a human T leukemia cell line and purified by gel filtration and isoelectric focusing, retained biological activity and was uniform with respect to size and charge. Binding of radiolabeled TCGF to TCGF-dependent cytolytic T cells occurred rapidly (within 15 rain at 37 degrees C) and was both saturable and largely reversible. In addition, at 37 degrees C, a receptor- and lysosome-dependent degradation of TCGF occurred. Radiolabeled TCGF binding was specific for activated, TCGF-responsive T cells. Whereas unstimulated lymphocytes of human or murine origin and lipopolysaccharide-activated B cell blasts expressed few if any detectable binding sites, lectin- or alloantigen-activated cells had easily detectable binding sites. Moreover, compared with lectin- or alloantigen-activated T cells, long-term TCGF-dependent cytolytic and helper T cell lines and TCGF-dependent neo-plastic T cell lines bound TCGF with a similar affinity (dissociation constant of 5-25 pM) and expressed a similar number of receptor sites per cell (5,000-15,000). In contrast, a number of TCGF-independent cell lines of T cell, B cell, or myeloid origin did not bind detectable quantities of radiolabeled TCGF. Binding of radiolabeled TCGF to TCGF-responsive cells was specific, in that among several growth factors and polypeptide hormones tested, only TCGF competed for binding. Finally, the relative magnitude of T cell proliferation induced by a given concentration of TCGF closely paralleled the fraction of occupied receptor sites. As the extent of T cell clonal expansion depends on TCGF and on the TCGF receptor, the dissection of the molecular events surrounding the interaction of TCGF and its receptor that these studies permit, should provide new insight into the hormonelike regulation of the immune response by this lymphokine

Efficient and Practical Transfer Hydrogenation of Ketones Catalyzed by a Simple Bidentate Mn−NHC Complex

Catalytic reductions of carbonyl‐containing compounds are highly important for the safe, sustainable, and economical production of alcohols. Herein, we report on the efficient transfer hydrogenation of ketones catalyzed by a highly potent Mn(I)−NHC complex. Mn−NHC 1 is practical at metal concentrations as low as 75 ppm, thus approaching loadings more conventionally reserved for noble metal based systems. With these low Mn concentrations, catalyst deactivation is found to be highly temperature dependent and becomes especially prominent at increased reaction temperature. Ultimately, understanding of deactivation pathways could help close the activity/stability‐gap with Ru and Ir catalysts towards the practical implementation of sustainable earth‐abundant Mn‐complexes

Time-Resolved Tracking of Mutations Reveals Diverse Allele Dynamics during Escherichia coli Antimicrobial Adaptive Evolution to Single Drugs and Drug Pairs

Understanding the evolutionary processes that lead to antibiotic resistance can help to achieve better treatment strategies. Yet, little is known about the dynamics of the resistance alleles during adaptation. Here, we use population sequencing to monitor genetic changes in putative resistance loci at several time-points during adaptive evolution experiments involving five different antibiotic conditions. We monitor the mutational spectra in lineages evolved to be resistant to single antibiotics [amikacin (AMK), chloramphenicol (CHL), and ciprofloxacin (CIP)], as well as antibiotic combinations (AMK + CHL and CHL + CIP). We find that lineages evolved to antibiotic combinations exhibit different resistance allele dynamics compared with those of single-drug evolved lineages, especially for a drug pair with reciprocal collateral sensitivity. During adaptation, we observed interfering, superimposing and fixation allele dynamics. To further understand the selective forces driving specific allele dynamics, a subset of mutations were introduced into the ancestral wild type enabling differentiation between clonal interference and negative epistasis

Functional Metagenomic Investigations of the Human Intestinal Microbiota

The human intestinal microbiota encode multiple critical functions impacting human health, including metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes accessible to pathogens. The complexity of this microbial community, its recalcitrance to standard cultivation, and the immense diversity of its encoded genes has necessitated the development of novel molecular, microbiological, and genomic tools. Functional metagenomics is one such culture-independent technique, used for decades to study environmental microorganisms, but relatively recently applied to the study of the human commensal microbiota. Metagenomic functional screens characterize the functional capacity of a microbial community, independent of identity to known genes, by subjecting the metagenome to functional assays in a genetically tractable host. Here we highlight recent work applying this technique to study the functional diversity of the intestinal microbiota, and discuss how an approach combining high-throughput sequencing, cultivation, and metagenomic functional screens can improve our understanding of interactions between this complex community and its human host

Recognition of differences in the capacity to deal with floods—A cross-country comparison of flood risk management

Flood risks worldwide are increasing due to climate change. Managing these risks is ever more necessary. Although flood risk management (FRM) is often understood as a technical challenge, it also involves decisions about the distribution of resources and risks in floods, which can be inherently unfair. People are disparately affected by floods due to their location. Because of their various socioeconomic and demographic characteristics, they also differ in their capacity to deal with floods. These differences need to be recognised in FRM to prevent disproportionate impacts on vulnerable communities. However, at present, a knowledge gap exists on how to make FRM more inclusive and just, and discussions on recognition justice in the context of FRM are scarce. This article therefore examines recognition of differences in the capacity of people to deal with floods in FRM in England (United Kingdom), Finland, Flanders (Belgium) and France. We analyse if, and how, these differences are recognised in FRM policy and practice and through decision-making procedures, drawing on examples from the implementation of five FRM strategies in each country (flood risk prevention, flood defence, flood risk mitigation, flood preparation and flood recovery). Furthermore, we aim to highlight opportunity spaces to strengthen recognition justice in future FRM

Choosing an Adequate Pesticide Delivery System for Managing Pathogens with Difficult Biologies: Case Studies on <em>Diplodia corticola, Venturia inaequalis</em> and <em>Erwinia amylovora</em>

With the challenges that negatively impact tree-based agriculture, landscapes and forests, such as climate change, plant pathogen and insect range expansion, invasive species and limited new pesticides, it is important to introduce new and effective tree protection options. In the last 20 years, pathogens that invade wood i.e. vascular tissues of trees causing wilt, yellowing, premature defoliation, cankers and tree death, have been on the rise. Diplodia corticola causes Bot canker of oak species which can kill trees diminishing the valuable ecological services they provide and reducing profits from wood and cork production. Since this and similar pathogens have difficult biologies because they reside in wood and cause severe internal damage and tree death, their management is difficult or inefficient with classical pesticide application methods that cannot reach and distribute the active ingredient in vascular wood tissues. As practical management options for this and other vascular tissue pathogens of trees are limited, we evaluated efficacy of several trunk injected fungicides in control of D. corticola and compared it with the efficacy of trunk injection of similar compounds for control of Venturia inaequalis and Erwinia amylovora, as two well-studied apple tree pathogens with different or partially similar lifestyles to D. corticola, respectively