Role of MHC-linked genes in autoantigen selection and renal disease in a murine model of systemic lupus erythematosus

We previously described a renal protective effect of factor B deficiency in MRL/lpr mice. Factor B is in the MHC cluster; thus, the deficient mice were H2b, the haplotype on which the knockout was derived, whereas the wild-type littermates were H2k, the H2 of MRL/lpr mice. To determine which protective effects were due to H2 vs factor B deficiency, we derived H2b congenic MRL/lpr mice from the 129/Sv (H2b) strain. Autoantibody profiling using autoantigen microarrays revealed that serum anti-Smith and anti-small nuclear ribonucleoprotein complex autoantibodies, while present in the majority of H2k/k MRL/lpr mice, were absent in the H2b/b MRL/lpr mice. Surprisingly, 70% of MRL/lpr H2b/b mice were found to be serum IgG3 deficient (with few to no IgG3-producing B cells). In addition, H2b/b IgG3-deficient MRL/lpr mice had significantly less proteinuria, decreased glomerular immune complex deposition, and absence of glomerular subepithelial deposits compared with MRL/lpr mice of any H2 type with detectable serum IgG3. Despite these differences, total histopathologic renal scores and survival were similar among the groups. These results indicate that genes encoded within or closely linked to the MHC region regulate autoantigen selection and isotype switching to IgG3 but have minimal effect on end-organ damage or survival in MRL/lpr mice.     

Numerical analysis of maximal bat performance in baseball

Metal baseball bats have been experimentally demonstrated to produce higher ball exit velocity (BEV) than wooden bats. In the United States, all bats are subject to BEV tests using hitting machines that rotate the bat in a horizontal plane. In this paper, a model of bat-ball impact was developed based on 3-D translational and rotational kinematics of a swing performed by high-level players. The model was designed to simulate the maximal performance of specific models of a wooden bat and a metal bat when swung by a player, and included material properties and kinematics specific to each bat. Impact dynamics were quantified using the finite element method (ANSYS/LSDYNA, version 6.1). Maximum BEV from both a metal (61.5 m/s) and a wooden (50.9 m/s) bat exceeded the 43.1 m/s threshold by which bats are certified as appropriate for commercial sale. The lower BEV from the wooden bat was attributed to a lower pre-impact bat linear velocity, and a more oblique impact that resulted in a greater proportion of BEV being lost to lateral and vertical motion. The results demonstrate the importance of factoring bat linear velocity and spatial orientation into tests of maximal bat performance, and have implications for the design of metal baseball bats.     

Managing ecological traps: Logging and sapsucker nest predation by bears

We tested the equal preference ecological trap hypothesis for breeding yellow-bellied sapsuckers (Sphyrapicus varius) along a time-since-harvest gradient (1–5 yr, 16–20 yr, 21–25 yr, and >60 yr) in selection system-logged hardwood forests in Algonquin Provincial Park, Ontario. Yellow-bellied sapsuckers preferred 1–5 year and >60-year-old cuts equally and more than 16–20 year and 21–25-year-old cuts. More-abundant arthropod food and/or higher-quality sap resources may have attracted yellow-bellied sapsuckers to 1–5 year and >60-year-old cuts. Only 52% of pairs raised fledglings in 1- to 5-year-old cuts during years when nest predation by American black bears (Ursus americanus) was common, the incidence of which was negatively related to increased availability of American beech (Fagus grandifolia) nuts from the previous autumn. By contrast, 88% of pairs raised fledglings in all years in >60-year-old cuts. One- to 5-year-old cuts were demographic sinks that represent equal-preference ecological traps in years when nest predation by bears was common, whereas >60-year-old cuts were always demographic sources. High-quality habitat cues for nesting yellow-bellied sapsuckers appear to be retained for 1–5 years after selection system logging but fail to deliver safe nest sites. Cavities excavated in heart-rot-infected nest trees are least likely to be depredated because cavity walls are typically harder and deter entry by depredating bears. Retaining more potential nest trees per ha at harvest (especially American beech with heart-rot) may increase the proportion of sapsucker nests that are excavated in bear-resistant trees, thereby reducing nest predation and increasing fecundity. © 2012 The Wildlife Society.     

Ontogenetic Changes in the Transport of Indol-3yl-acetic Acid into Maize Roots from the Shoot and Caryopsis

The quantities of endogenous indol-3yl-acetic acid (IAA) in endosperms and scutella of 6-day-old maize seedlings (Zea mays L. cv Giant White Horsetooth) were determined by a fluorimetric method. Endosperms were found to contain 33.4 nanograms IAA per plant, and scutella 7.5 nanograms IAA per plant. [5-³H]IAA applied to endosperms of 6-day-old seedlings moved into the roots and radioactivity accumulated at the apex of the primary root within 8 hours. Two to 7-day-old seedlings were treated simultaneously with [5-³H]IAA in the endosperm and [2-¹⁴C] IAA on the shoot apex. The patterns of transport into the root were found to change during ontogeny: in successively older plants, transport from the shoot into the roots increased relative to transport from the endosperm into the roots. The auxin required for the growth of maize roots could, therefore, partially be contributed by the shoot and endosperm. Ontogenetic changes in the relative importance of these two supplies could be of significance for the integration of growth and development between shoot and root.     

Key Golgi factors for structural and functional maturation of bunyamwera virus

Several complex enveloped viruses assemble in the membranes of the secretory pathway, such as the Golgi apparatus. Among them, bunyaviruses form immature viral particles that change their structure in a trans-Golgi-dependent manner. To identify key Golgi factors for viral structural maturation, we have purified and characterized the three viral forms assembled in infected cells, two intracellular intermediates and the extracellular mature virion. The first viral form is a pleomorphic structure with fully endo-beta-N-acetylglucosaminidase H (Endo-H)-sensitive, nonsialylated glycoproteins. The second viral intermediate is a structure with hexagonal and pentagonal contours and partially Endo-H-resistant glycoproteins. Sialic acid is incorporated into the small glycoprotein of this second viral form. Growing the virus in glycosylation-deficient cells confirmed that acquisition of Endo-H resistance but not sialylation is critical for the trans-Golgi-dependent structural maturation and release of mature viruses. Conformational changes in viral glycoproteins triggered by changes in sugar composition would then induce the assembly of a compact viral particle of angular contours. These structures would be competent for the second maturation step, taking place during exit from cells, that originates fully infectious virions.     

The extreme carboxyl terminus of the equine herpesvirus 1 homolog of herpes simplex virus VP16 is essential for immediate-early gene activation.

Gene 12 of equine herpesvirus 1 (EHV-1), the homolog of herpes simplex virus (HSV) VP16 (alpha TIF, Vmw65), was cloned into a eukaryotic expression vector by PCR and used in transactivation studies of both the EHV-1 and HSV-1 IE1 promoters. Results demonstrated that the product of gene 12 is a potent transactivator of immediate-early gene expression of both viruses, which requires sequences in the upstream HSV-1 promoter for activity. Mutational analysis of the gene 12 open reading frame indicated that removal of the C-terminal 7 amino acids, which contain a short region of homology with the extreme C terminus of VP16, inactivated the protein. Within this region, only a single methionine residue appeared to be essential for activity, implying that gene 12 may have a modular array of organization similar to that of VP16. However, fusion of the gene 12 C terminus to a truncated form of VP16, which contained the complex formation domain, did not restore activity to the HSV-1 protein. These data demonstrate that the EHV-1 immediate-early transactivator may not be functionally colinear with VP16, with transactivation requiring both the C terminus and another region(s) present within the N-terminal portion.     

Widespread Recombination,Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections

Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.     

Entrainment of circadian programs

Of the three defining properties of circadian rhythmicity--persisting free-running rhythm, temperature compensation, and entrainment--the last is often poorly understood by many chronobiologists. This paper gives an overview of entrainment. Where have we been? Where are we now? Whence should we be going? Particular emphasis is given to a discussion of the Discrete vs. Continuous models for entrainment. We provide an integrated mechanism for entrainment from a limit-cycle perspective.