From “Us vs. Them” to “Shared Risk”: Can Animals Help Link Environmental Factors to Human Health?

Linking human health risk to environmental factors can be a challenge for clinicians, public health departments, and environmental health researchers. While it is possible that nonhuman animal species could help identify and mitigate such linkages, the fields of animal and human health remain far apart, and the prevailing human health attitude toward disease events in animals is an “us vs. them” paradigm that considers the degree of threat that animals themselves pose to humans. An alternative would be the development of the concepts of animals as models for environmentally induced disease, as well as potential “sentinels” providing early warning of both noninfectious and infectious hazards in the environment. For such concepts to truly develop, critical knowledge gaps need to be addressed using a “shared risk” paradigm based on the comparative biology of environment–host interactions in different species.     

Derepression of Synthesis of the Aminoacyl-Transfer Ribonucleic Acid Synthetases for the Branched-Chain Amino Acids of Escherichia coli

The kinetics of derepression of valyl-, isoleucyl-, and leucyl-transfer ribonucleic acid (tRNA) synthetase formation was examined during valine-, isoleucine-, and leucine-limited growth. When valine was limiting growth, valyl-tRNA synthetase formation was maximally derepressed within 5 min, whereas the rates of synthesis of isoleucyl-, and leucyl-tRNA synthetases were unchanged. Isoleucine-restricted growth caused a maximal derepression of isoleucyl-tRNA synthetase formation in 5 min and derepression of valyl-tRNA synthetase formation in 15 min with no effect on leucyl-tRNA synthetase formation. When leucine was limiting growth, leucyl-tRNA synthetase formation was immediately derepressed, whereas valyl- and isoleucyl-tRNA synthetase formation was unaffected by manipulation of the leucine supply to the cells. These results support our previous findings that valyl-tRNA synthetase formation is subject to multivalent repression control by both isoleucine and valine. In contrast, repression control of iso-leucyl- and leucyl-tRNA synthetase formation is specifically mediated by the supply of the cognate amino acid.     

Acceleration of cyanobacterial dominance in north temperate‐subarctic lakes during the Anthropocene

Increases in atmospheric temperature and nutrients from land are thought to be promoting the expansion of harmful cyanobacteria in lakes worldwide, yet to date there has been no quantitative synthesis of long‐term trends. To test whether cyanobacteria have increased in abundance over the past ~ 200 years and evaluate the relative influence of potential causal mechanisms, we synthesised 108 highly resolved sedimentary time series and 18 decadal‐scale monitoring records from north temperate‐subarctic lakes. We demonstrate that: (1) cyanobacteria have increased significantly since c. 1800 ce , (2) they have increased disproportionately relative to other phytoplankton, and (3) cyanobacteria increased more rapidly post c. 1945 ce . Variation among lakes in the rates of increase was explained best by nutrient concentration (phosphorus and nitrogen), and temperature was of secondary importance. Although cyanobacterial biomass has declined in some managed lakes with reduced nutrient influx, the larger spatio‐temporal scale of sedimentary records show continued increases in cyanobacteria throughout the north temperate‐subarctic regions.     

Merging theory and mechanism in studies of gynodioecy

In gynodioecious species, females and hermaphrodites coexist and the genetics of sex determination is usually nuclear cytoplasmic. Maintaining nuclear-cytoplasmic gynodioecy requires polymorphism for the feminizing genes (contained in the mitochondria) and the genes that restore male fertility (contained in the nucleus). This complex polymorphism depends, in part, on there being negative pleiotropic effects (i.e. costs) of the nuclear restorer alleles. Here, we combine information from theoretical studies and studies on the molecular action of restorer alleles in crops to interpret the probable costs of such alleles, and suggest how various aspects of the theoretical models could be tested. In doing so, we highlight how crops can be used to address evolutionary questions about the maintenance of nuclear-cytoplasmic gynodioecy.     

Structure of Ptr ToxA: an RGD-containing host-selective toxin from Pyrenophora tritici-repentis

Tan spot of wheat (Triticum aestivum), caused by the fungus Pyrenophora tritici-repentis, has significant agricultural and economic impact. Ptr ToxA (ToxA), the first discovered proteinaceous host-selective toxin, is produced by certain P. tritici-repentis races and is necessary and sufficient to cause cell death in sensitive wheat cultivars. We present here the high-resolution crystal structure of ToxA in two different crystal forms, providing four independent views of the protein. ToxA adopts a single-domain, beta-sandwich fold of novel topology. Mapping of the existing mutation data onto the structure supports the hypothesized importance of an Arg-Gly-Asp (RGD) and surrounding sequence. Its occurrence in a single, solvent-exposed loop in the protein suggests that it is directly involved in recognition events required for ToxA action. Furthermore, the ToxA structure reveals a surprising similarity with the classic mammalian RGD-containing domain, the fibronectin type III (FnIII) domain: the two topologies are related by circular permutation. The similar topologies and the positional conservation of the RGD-containing loop raises the possibility that ToxA is distantly related to mammalian FnIII proteins and that to gain entry it binds to an integrin-like receptor in the plant host.     

Kinetics in signal transduction pathways involving promiscuous oligomerizing receptors can be determined by receptor specificity: apoptosis induction by TRAIL

Here we show by computer modeling that kinetics and outcome of signal transduction in case of hetero-oligomerizing receptors of a promiscuous ligand largely depend on the relative amounts of its receptors. Promiscuous ligands can trigger the formation of nonproductive receptor complexes, which slows down the formation of active receptor complexes and thus can block signal transduction. Our model predicts that increasing the receptor specificity of the ligand without changing its binding parameters should result in faster receptor activation and enhanced signaling. We experimentally validated this hypothesis using the cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its four membrane-bound receptors as an example. Bypassing ligand-induced receptor hetero-oligomerization by receptor-selective TRAIL variants enhanced the kinetics of receptor activation and augmented apoptosis. Our results suggest that control of signaling pathways by promiscuous ligands could result in apparent slow biological kinetics and blocking signal transmission. By modulating the relative amount of the different receptors for the ligand, signaling processes like apoptosis can be accelerated or decelerated and even inhibited. It also implies that more effective treatments using protein therapeutics could be achieved simply by altering specificity.     

Evidence for persistent, occult infection in neonatal macaques following perinatal transmission of simian-human immunodeficiency virus SF162P3

To model human immunodeficiency virus (HIV) perinatal transmission, we studied infection of simian-human immunodeficiency virus (SHIV) SF162P3 in 10 pregnant Macaca nemestrina females and their offspring. Four of nine infants born to and suckled by these dams had evidence of infection, a transmission rate of 44.4% (95% confidence interval, 13.7% to 78.8%). We quantified transplacentally acquired and de novo Env-specific immunoglobulin G (IgG), IgM, and neutralizing antibodies in newborns. Transmission of escape variants was confirmed. In utero infection (n = 1) resulted in high viremia, depletion of peripheral CD4+ T cells, and rapid evolution of env in blood and tissues. Peripartum or postpartum SHIV infection (n = 3) resulted in postacute viral control that was undetectable by very sensitive multiplex PCR, despite increasing antibodies. Seropositive infants with highly controlled viremia had homogeneous peripheral blood env sequences, and their tissues had <3 copies per million cells. A high incidence of seropositive virus-low or -negative SHIV infection in infant macaques has implications for HIV type 1 perinatal transmission and detection.     

Distinctive ganglioside patterns revealed by anti-ganglioside antibody binding to differentiating CG-4 oligodendrocytes

Oligodendrocytes are central nervous system glial cells responsiblefor myelination of neuronal axons. During brain developmentoligodendrocyte progenitor cells progress through a series ofmorphologically and immunohistochemically distinct differentiationsteps leading to mature myelin-producing oligodendrocytes. Muchof this same differentiation sequence is expressed in vitroby primary oligodendrocyte progenitor cells, and by the clonalprogenitor cell line CG-4. We report the use of highly specificmonoclonal antibodies against GM1, GDla, GD1b, GT1b, and GQ1bto determine major brain ganglioside expression and morphologicaldistribution during CG-4 differentiation in vitro. Prominentanti-GD1b antibody staining defined a highly arborized intermediatestage of oligodendrocyte differentiation. In contrast, anti-GT1bantibody bound to discrete patches on the cell bodies of earlyprogenitor cells and more mature oligodendrocytes, and to sitesof progenitor arborization. The other anti-ganglioside antibodiestested did not bind above background levels. Cells with anti-GD1bantibody binding and morphology similar to those in differentiatingCG-4 cells were detected in rat brain primary cell culturesenriched in oligodendrocyte precursors. The remarkably distinctiveganglioside immunoreactivhy on differentiating oligodendrocytessuggests the possibility of a functional role for their surfaceexpression. gangliosides glycosphingolipids oligodendrocytes myelination differentiation     

Inertial sensor based method for identifying spherical joint center of rotation

The miniaturized wireless inertial measurement unit (IMU) technology and algorithms presented herein promote rapid and accurate predictions of the center-of-rotation (CoR) for ball/spherical joints. The algorithm improves upon existing IMU-based methods by directly utilizing the measured acceleration and angular velocity provided by the IMU to deduce the CoR in lieu of relying on error-prone velocity and position estimates. Results demonstrate that this new method resolves the position of the CoR to within a 3 mm sphere of the true CoR determined by a precision coordinate measuring machine. Such accuracy may render this method attractive for broad use in field, laboratory and clinical settings requiring non-invasive and rapid estimates of joint CoR.