Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling

A healthy individual can mount an immune response to exogenous pathogens while avoiding an autoimmune attack on normal tissues. The ability to distinguish between self and non-self is called 'immunological tolerance' and, for T lymphocytes, involves the generation of a diverse pool of functional T cells through positive selection and the removal of overtly self-reactive thymocytes by negative selection during T-cell ontogeny. To elucidate how thymocytes arrive at these cell fate decisions, here we have identified ligands that define an extremely narrow gap spanning the threshold that distinguishes positive from negative selection. We show that, at the selection threshold, a small increase in ligand affinity for the T-cell antigen receptor leads to a marked change in the activation and subcellular localization of Ras and mitogen-activated protein kinase (MAPK) signalling intermediates and the induction of negative selection. The ability to compartmentalize signalling molecules differentially in the cell endows the thymocyte with the ability to convert a small change in analogue input (affinity) into a digital output (positive versus negative selection) and provides the basis for establishing central tolerance.     

Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity

The haemagglutinin (HA) glycoproteins of influenza virus membranes are responsible for binding viruses to cells by interacting with membrane receptor molecules which contain sialic acid (for review see ref. 1). This interaction is known to vary in detailed specificity for different influenza viruses (see, for example, refs 2-4) and we have attempted to identify the sialic acid binding site of the haemagglutinin by comparing the amino acid sequences of haemagglutinins with different binding specificities. We present here evidence that haemagglutinins which differ in recognizing either NeuAc alpha 2 leads to 3Gal- or NeuAc alpha 2 leads to 6Gal- linkages in glycoproteins also differ at amino acid 226 of HA1. This residue is located in a pocket on the distal tip of the molecule, an area previously proposed from considerations of the three-dimensional structure of the haemagglutinin to be involved in receptor binding.     

A long-term survey of spring monarch butterflies in north-central Florida

Long-term springtime counts of immature and adult monarch butterflies and their Asclepias humistrata host plants in north-central Florida reveal a close relationship between the milkweed’s phenology and the butterfly’s spring remigration from Mexico. Remigrant adults arrive after most frosts occur and as the milkweeds are flourishing but before the plants begin to senesce. The peak of adult arrival is during the first few days in April; the eggs that are laid during this peak develop through April, leading to a second peak in adult abundance in early May. These newly emerged adults continue the migration northward. In addition to assessing the phenology of annual events, our long-term survey, with regular monitoring from 1994–2017, has enabled us to evaluate long-term trends. Both adults and immatures have declined in abundance from 1985 to 2017; since 2005, both have declined by around 80%. This decline has occurred concurrently with the decline in the number of monarchs at their Mexican overwintering sites.     

The persistence of T cell memory

T cell memory is a crucial feature of the adaptive immune system in the defense against pathogens. During the last years, numerous studies have focused their efforts on uncovering the signals, inflammatory cues, and extracellular factors that support memory differentiation. This research is beginning to decipher the complex gene network that controls memory programming. However, how the different signals, that a T cell receives during the process of differentiation, interplay to trigger memory programming is still poorly defined. In this review, we focus on the most recent advances in the field and discuss how T cell receptor signaling and inflammation control CD8 memory differentiation.     

Anthelmintic activity of tioxidazole (Sch 21480) against gastrointestinal roundworms

Summary Methyl-6-propoxybenzothiazo-2-carbamate (tioxidazole) has broad spectrum activity against gastrointestinal nematodes.     

Studies on the action of X-rays on aqueous solutions of nucleic acids and some nucleotides

Zusammenfassung Die Wirkung von Röntgenstrahlen (200 kV) auf wässerige Lösungen von Nukleinsäuren und Nukleotiden wurde unter besonderer Berücksichtigung des Einflusses von molekularem Sauerstoff und Wasserstoffsuperoxyd untersucht. Der so gefundene, nach der Bestrahlung einsetzende Abfall der Viskosität von D.N.A.-Lösungen (after-effect) kann als Hydrolyse der durch die Bestrahlung labilisierten Kohlenstoff-Phosphat-Bindungen angesehen werden. Untersuchungen über die Hydrolyse von bestrahlten Nukleotiden, -P.N.A.- und D.N.A.-Lösungen stehen in vollem Einklang mit obiger Annahme.     

The role of the adrenal gland in the control of intestinal absorption of macromolecules by the young rat

Résumé L'absorption de¹²⁵I polyvinyl pyrrolidone K. 60 par l'intestin grêle a été mesurée dans des rats dont les capsules surrénales avaient été enlevées à 3, 14, 16, 18 et 23 jours après la mise bas. Des animaux témoins ont été opérés sans ablation des capsules surrénales et ils n'ont plus absorbé le PVP 20 à 21 jours après la mise bas, mais lorsque les capsules surrénales furent enlevées avant 23 jours après la mise bas, le PVP a été absorbé environs 4 jours au-delà des délais témons.     

Dinitrogen fixation by a thermophilic methanogenic bacterium

Methanogenic bacteria are known to use NH+4 as a nitrogen source for growth. Previous work with an impure methanogenic culture suggested that a methanogen might fix atmospheric dinitrogen as a nitrogen source, but no further work on this phenomenon has been documented. We have now examined the use of N2 by Methanococcus thermolithotrophicus and find that the organism can grow well, with multiple transfers, in medium having N2 as the source of nitrogen. Control cultures without N2 and containing less than 0.1 mM NH+4 do not grow. Growth yields with N2 are on the average one-third those with NH+4, suggesting that, as in other nitrogen-fixing organisms, this bacterium requires a large amount of ATP for the reduction to occur. After growing in NH+4-containing medium, a long lag is observed before growth begins with N2 as the nitrogen source; the NH+4 levels must be very low for growth to begin. Cells grown in N2-fixing conditions reduce acetylene to ethylene. The discovery of a nitrogen-fixing archaebacterium has important implications for studies on the evolution of nitrogenase, and the fact that M. thermolithotrophicus nitrogenase is active at 64 degrees C suggests that a novel enzyme is involved.