Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria

Background

TNF-related lymphotoxin α (LTα) is essential for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a second arm of LTα-signaling essential for ECM development through LTβ-R, receptor of LTα1β2 heterotrimer.

Methodology/Principal Findings

LTβR deficient mice did not develop the neurological signs seen in PbA induced ECM but died at three weeks with high parasitaemia and severe anemia like LTαβ deficient mice. Resistance of LTαβ or LTβR deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin⁺ CD8⁺ T cells, and their ICAM-1 expression were clearly attenuated in the brain of resistant mice. An essential contribution of LIGHT, another LTβR ligand, could be excluded, as LIGHT deficient mice rapidly succumbed to ECM.

Conclusions/Significance

LTβR expressed on radioresistant resident stromal, probably endothelial cells, rather than hematopoietic cells, are essential for the development of ECM, as assessed by hematopoietic reconstitution experiment. Therefore, the data suggest that both functional LTβR and TNFR2 signaling are required and non-redundant for the development of microvascular pathology resulting in fatal ECM.     

Impact of Herbicides on Heterodera glycines Susceptible and Resistant Soybean Cultivars

Several abiotic and biotic stresses can affect soybean in a growing season. Heterodera glycines, soybean cyst nematode, reduces yield of soybean more than any other pathogen in the United States. Field and greenhouse studies were conducted to determine whether preemergence and postemergence herbicides modified the reproduction of H. glycines, and to determine the effects of possible interactive stresses caused by herbicides and H. glycines on soybean growth and yield. Heterodera glycines reproduction factor (Rf) generally was less on resistant than susceptible cultivars, resulting in a yield advantage for resistant cultivars. The yield advantage of resistant cultivars was due to more pods per plant on resistant than susceptible cultivars. Pendimethalin reduced H. glycines Rf on the susceptible cultivars in 1998 at Champaign, Illinois, and in greenhouse studies reduced dry root weight of H. glycines-resistant and susceptible cultivars, therefore reducing Rf on the susceptible cultivars. The interactive stresses from acifluorfen or imazethapyr and H. glycines reduced the dry shoot weight of the resistant cultivar Jack in a greenhouse study. Herbicides did not affect resistant cultivars'' ability to suppress H. glycines Rf; therefore, growers planting resistant cultivars should make herbicide decisions based on weeds present and cultivar tolerance to the herbicide.     

The basal proton conductance of skeletal muscle mitochondria from transgenic mice overexpressing or lacking uncoupling protein-3.

The ability of native uncoupling protein-3 (UCP3) to uncouple mitochondrial oxidative phosphorylation is controversial. We measured the expression level of UCP3 and the proton conductance of skeletal muscle mitochondria isolated from transgenic mice overexpressing human UCP3 (UCP3-tg) and from UCP3 knockout (UCP3-KO) mice. The concentration of UCP3 in UCP3-tg mitochondria was approximately 3 microg/mg protein, approximately 20-fold higher than the wild type value. UCP3-tg mitochondria had increased nonphosphorylating respiration rates, decreased respiratory control, and approximately 4-fold increased proton conductance compared with the wild type. However, this increased uncoupling in UCP3-tg mitochondria was not caused by native function of UCP3 because it was not proportional to the increase in UCP3 concentration and was neither activated by superoxide nor inhibited by GDP. UCP3 was undetectable in mitochondria from UCP3-KO mice. Nevertheless, UCP3-KO mitochondria had unchanged respiration rates, respiratory control ratios, and proton conductance compared with the wild type under a variety of assay conditions. We conclude that uncoupling in UCP3-tg mice is an artifact of transgenic expression, and that UCP3 does not catalyze the basal proton conductance of skeletal muscle mitochondria in the absence of activators such as superoxide.     

Abrupt changes in the composition and function of fungal communities along an environmental gradient in the high Arctic

Fungi play a key role in soil–plant interactions, nutrient cycling and carbon flow and are essential for the functioning of arctic terrestrial ecosystems. Some studies have shown that the composition of fungal communities is highly sensitive to variations in environmental conditions, but little is known about how the conditions control the role of fungal communities (i.e., their ecosystem function). We used DNA metabarcoding to compare taxonomic and functional composition of fungal communities along a gradient of environmental severity in Northeast Greenland. We analysed soil samples from fell fields, heaths and snowbeds, three habitats with very contrasting abiotic conditions. We also assessed within‐habitat differences by comparing three widespread microhabitats (patches with high cover of Dryas, Salix, or bare soil). The data suggest that, along the sampled mesotopographic gradient, the greatest differences in both fungal richness and community composition are observed amongst habitats, while the effect of microhabitat is weaker, although still significant. Furthermore, we found that richness and community composition of fungi are shaped primarily by abiotic factors and to a lesser, though still significant extent, by floristic composition. Along this mesotopographic gradient, environmental severity is strongly correlated with richness in all fungal functional groups: positively in saprotrophic, pathogenic and lichenised fungi, and negatively in ectomycorrhizal and root endophytic fungi. Our results suggest complex interactions amongst functional groups, possibly due to nutrient limitation or competitive exclusion, with potential implications on soil carbon stocks. These findings are important in the light of the environmental changes predicted for the Arctic.     

Molecular phylogenetics and biogeography of Neotropical piping guans (Aves: Galliformes): Pipile Bonaparte, 1856 is synonym of Aburria Reichenbach, 1853

The Cracidae are Neotropical galliform birds with 11 genera currently recognized. To investigate the questioned validity of Pipile Bonaparte, 1856 and the monotypic Aburria Reichenbach, 1853 as separate genera, we gathered data from 2727 bp of mitochondrial DNA (cytochrome b, ND2 and control region) and 151 osteological characters. Our phylogenetic analyses of DNA sequences indicated that Aburria aburri is embedded within Pipile. Also, genetic distances between Aburria and any Pipile species are equivalent to the distances estimated for other congeneric cracid species, which genus status is not doubtful. Although the osteological characters do not have phylogenetic signal to solve the phylogenetic relationships at species level, five synapomorphies were found for Aburria and Pipile. Therefore, we suggest that Pipile should be merged with Aburria, which is the oldest described genus. We estimated that speciation in this group occurred in the Plio-Pleistocene, concordant with other birds, primates and rodents that have similar geographic distribution, and proposed a diversification hypothesis based on the occurrence of sea transgressions and the formation of the Amazon Lagoon. Therefore, we conclude that these palaeogeographic events may have contributed to Neotropical taxa diversification to a greater extent than previously suspected.     

Gene algebra from a genetic code algebraic structure

By considering two important factors involved in the codon-anticodon interactions, the hydrogen bond number and the chemical type of bases, a codon array of the genetic code table as an increasing code scale of interaction energies of amino acids in proteins was obtained. Next, in order to consecutively obtain all codons from the codon AAC, a sum operation has been introduced in the set of codons. The group obtained over the set of codons is isomorphic to the group (Z₆₄, +) of the integer module 64. On the Z₆₄-algebra of the set of 64^N codon sequences of length N, gene mutations are described by means of endomorphisms f:(Z₆₄)^N→(Z₆₄)^N. Endomorphisms and automorphisms helped us describe the gene mutation pathways. For instance, 77.7% mutations in 749 HIV protease gene sequences correspond to unique diagonal endomorphisms of the wild type strain HXB2. In particular, most of the reported mutations that confer drug resistance to the HIV protease gene correspond to diagonal automorphisms of the wild type. What is more, in the human beta-globin gene a similar situation appears where most of the single codon mutations correspond to automorphisms. Hence, in the analyses of molecular evolution process on the DNA sequence set of length N, the Z₆₄-algebra will help us explain the quantitative relationships between genes.     

A genetic code Boolean structure. II. The genetic information system as a Boolean information system

A Boolean structure of the genetic code where Boolean deductions have biological and physicochemical meanings was discussed in a previous paper. Now, from these Boolean deductions we propose to define the value of amino acid information in order to consider the genetic information system as a communication system and to introduce the semantic content of information ignored by the conventional information theory. In this proposal, the value of amino acid information is proportional to the molecular weight of amino acids with a proportional constant of about 1.96×10²⁵ bits per kg. In addition to this, for the experimental estimations of the minimum energy dissipation in genetic logic operations, we present two postulates: (1) the energy E _i (i = 1, 2, ..., 20) of amino acids in the messages conveyed by proteins is proportional to the value of information, and (2) amino acids are distributed according to their energy E _i so the amino acid population in proteins follows a Boltzmann distribution. Specifically, in the genetic message carried by the DNA from the genomes of living organisms, we found that the minimum energy dissipation in genetic logic operations was close to kTLn(2) joules per bit.     

Identification of tilapia ghrelin and its effects on growth hormone and prolactin release in the tilapia,Oreochromis mossambicus

We have identified ghrelin and cDNA encoding precursor protein from the stomach of a euryhaline tilapia, Oreochromis mossambicus. The sequence of 20-amino acid tilapia ghrelin is GSSFLSPSQKPQNKVKSSRI. The third serine residue was modified by n-decanoic acid. The carboxyl-terminal end of the peptide possessed an amide structure. RT-PCR analysis revealed high levels of gene expression in the stomach and low levels in the brain, kidney and gill. Tilapia ghrelin stimulated growth hormone (GH) and prolactin (PRL) release from the organ-cultured tilapia pituitary at a dose of 10 nM. Thus, a novel regulatory mechanism of GH secretion by gastric ghrelin seems to be conserved in the tilapia. Stimulation of PRL release by homologous ghrelin has been reported in human, bullfrog and eel, and suggests the presence of growth hormone secretagogue receptor not only on somatotrophs but also on PRL cells of the tilapia pituitary.     

Evidence that signal transduction for osmoreception is mediated by stretch-activated ion channels in tilapia

Prolactin (PRL) playsa central role in the freshwater osmoregulation of teleost fish,including the tilapia (Oreochromis mossambicus). Consistentwith this action, PRL release from the tilapia pituitary increases asextracellular osmolality is reduced both in vitro and in vivo.Dispersed tilapia PRL cells were incubated in a perfusion chamber thatallowed simultaneous measurements of cell volume and PRL release.Intracellular Ca²⁺ concentrations were measured from fura2-loaded PRL cells treated in a similar way. Gadolinium(Gd³⁺), known to block stretch-activated cation channels,inhibited hyposmotically induced PRL release in a dose-related mannerwithout preventing cell swelling. Nifedipine, an L-typeCa²⁺ channel blocker, did not prevent the increase in PRLrelease during hyposmotic stimulation. A high, depolarizingconcentration of KCl induced a transient and marked increase ofintracellular Ca²⁺ and release of PRL but did not preventthe rise in intracellular Ca²⁺ and PRL release evoked byexposure to hyposmotic medium. These findings suggest that a decreasein extracellular osmolality stimulates PRL release through the openingof stretch-activated ion channels, which allow extracellularCa²⁺ to enter the cell when it swells.