Diversity biases in terrestrial mammalian assemblages and quantifying the differences between museum collections and published accounts: A case study from the Miocene of Nevada

Understanding diversity through time in the fossil record has primarily relied on the raw count of species within a given time interval, or species richness. These estimates are often derived from published fossil data, and standardized for sample size or geographic area. However, most methods that standardize richness by sample size are sensitive to changes in evenness, which introduces a potential problem with relying on published records: published accounts could be more even than the museum collections from which they are drawn. We address this bias in the context of mammalian paleodiversity, comparing published and museum collections of the Hemphillian Thousand Creek fauna to those of the Barstovian Virgin Valley fauna. We rarified specimen data, both number of identified specimens (NISP) and minimum number of individuals (MNI), and presence/absence data to compare published and museum data within and between faunas. Within faunas, published numbers of specimens are more even than museum samples, but the difference for localities in Virgin Valley is not significant. Neither published nor museum numbers of specimens indicate a significant difference between faunas, but the diversity pattern is reversed between the two data sets. Presence/absence rarefactions show no differences between sources; here, published data adequately sample the underlying museum records. Specimen-based evenness is not accurate in the published sample, and therefore we suggest that future studies of diversity in terrestrial mammalian assemblages must assess unpublished collections. Additionally, NISP data for Thousand Creek are more even than MNI data, suggesting that relying solely on NISP for assessing species diversity can also be misleading. Because publication bias alters richness and evenness, diversity estimates using published data must be circumspect about data sources.     

Evaluating the importance of within- and between-host selection pressures on the evolution of chronic pathogens

Infectious pathogens compete and are subject to natural selection at multiple levels. For example, viral strains compete for access to host resources within an infected host and, at the same time, compete for access to susceptible hosts within the host population. Here we propose a novel approach to study the interplay between within- and between-host competition. This approach allows for a single host to be infected by and transmit two strains of the same pathogen. We do this by nesting a model for the host-pathogen dynamics within each infected host into an epidemiological model. The nesting of models allows the between-host infectivity and mortality rates suffered by infected hosts to be functions of the disease progression at the within-host level. We present a general method for computing the basic reproduction ratio of a pathogen in such a model. We then illustrate our method using a basic model for the within-host dynamics of viral infections, embedded within the simplest susceptible-infected (SI) epidemiological model. Within this nested framework, we show that the virion production rate at the level of the cell-virus interaction leads, via within-host competition, to the presence or absence of between-host level competitive exclusion. In particular, we find that in the absence of mutation the strain that maximizes between-host fitness can outcompete all other strains. In the presence of mutation we observe a complex invasion landscape showing the possibility of coexistence. Although we emphasize the application to human viral diseases, we expect this methodology to be applicable to be many host-parasite systems.     

Immunological responses and viral modulatory effects of vaccination with recombinant modified vaccinia virus Ankara (rMVA) expressing structural and regulatory transgenes of simian immunodeficiency virus (SIVmac32H/J5M)

Background The immunogenicity and protective efficacy of recombinant modified vaccinia virus Ankara (rMVA) vectors expressing structural (gag/pol, env) and regulatory (tat, rev, nef) genes of SIVmac251/32H‐J5 (rMVA‐J5) were assessed. Methods Immunization with rMVA constructs (2.5 × 10⁷ IU) 32, 20 and 8 weeks pre‐challenge was compared with 32 and 20 weeks but with a final boost 8 weeks pre‐challenge with 2 × 10⁶ fixed‐inactivated HSC‐F4 cells infected with SIVmac32H. Controls received rMVA vectors expressing an irrelevant transgene or were naïve challenge controls. All received 10 MID₅₀ SIVmac32H/J5 intravenously. Results Vaccinates immunized with rMVA‐J5 exhibited significant, albeit transient, control of peak primary viraemia despite inconsistent and variable immune responses elicted by vaccination. Humoral and cellular responses to Env were most consistent, with lower responses to Nef, Rev and Tat. Increasing titres of anti‐vaccinia neutralizing antibodies reflected the number and dose of rMVA inoculations. Conclusions Improved combinations of viral vectors are required to elicit appropriate immune responses to control viral replication.     

Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6-wk translational research study

Evidence from rodent studies indicates that the beta-cell-derived neurohormone amylin exerts multiple effects on eating behavior, including reductions in meal size, intake of highly palatable foods, and stress-induced sucrose consumption. To assess the effect of amylin agonism on human eating behavior we conducted a randomized, blinded, placebo-controlled, multicenter study investigating the effects of the amylin analog pramlintide on body weight, 24-h caloric intake, portion sizes, "fast food" intake, and perceived control of eating in 88 obese subjects. After a 2-day placebo lead-in, subjects self-administered pramlintide (180 microg) or placebo by subcutaneous injection 15 min before meals for 6 wk without concomitant lifestyle modifications. Compared with placebo, pramlintide treatment elicited significant mean reductions from baseline in body weight on day 44 (-2.1 +/- 0.3 vs. +0.1 +/- 0.4%, P < 0.001), 24-h caloric intake (-990 +/- 94 vs. -243 +/- 126 kcal on day 3, P < 0.0001; -680 +/- 86 vs. -191 +/- 161 kcal on day 43, P < 0.01), portion sizes, and caloric intake at a "fast food challenge" (-385 +/- 61 vs. -109 +/- 88 kcal on day 44, P < 0.05). Pramlintide treatment also improved perceived control of eating, as demonstrated by a 45% placebo-corrected reduction in binge eating scores (P < 0.01). The results of this translational research study confirm in humans various preclinical effects of amylin agonism, demonstrating that pramlintide-mediated weight loss in obese subjects is accompanied by sustained reductions in 24-h food intake, portion sizes, fast food intake, and binge eating tendencies.     

Altered inflammatory gene expression underlies increased susceptibility to murine postoperative ileus with advancing age

Susceptibility to postoperative ileus following abdominal surgery increases with advancing age. The mechanisms underlying this phenomenon are unknown. This study compares functional and molecular endpoints between young-adult (2 mo old), middle-aged (15 mo old), and elderly mice (26-30 mo old) to identify potential mechanisms. Susceptibility to ileus was assessed by measuring gastrointestinal transit (geometric center) 24 h after anesthesia, laparotomy, and light manipulation (LM) of the small bowel. Proinflammatory (IL-6, COX-2, inducible nitric oxide synthase) and anti-inflammatory (IL-10, heme oxygenase-1) gene and protein expressions were determined by real time RT-PCR, Western blot, and ELISA. LM did not alter gastrointestinal transit in young animals (geometric center = 8.8 +/- 0.9), but transit was increasingly delayed in middle-aged (6.9 +/- 0.8, P = 0.03) and elderly animals (4.7 +/- 0.6, P = 0.013). Despite the lack of LM effect on transit in young mice, IL-6 and COX-2 mRNA expressions were significantly increased postoperatively (165 +/- 24-fold and 2.9 +/- 0.3-fold, respectively). Expressions were increased further in middle-aged mice (1,103 +/- 187-fold; 4.4 +/- 0.7-fold) and further still in elderly mice (1,218 +/- 168-fold; 6.9 +/- 0.3-fold). IL-10 and heme oxygenase-1 gene expressions were also elevated postoperatively in young mice (4.8 +/- 0.5-fold and 13.0 +/- 1.3-fold, respectively) and were further increased in middle-aged mice (7.5 +/- 0.6-fold; 21.8 +/- 3.2-fold). However, inductions in elderly mice were significantly blunted (5.8 +/- 0.9-fold; 16.9 +/- 0.8-fold). There is both an age-dependent increase in the proinflammatory mediator expression and an age-dependent decrease in anti-inflammatory mediator expressions following minor insult to the bowel. Such imbalances between pro- and anti-inflammatory mechanisms may form the basis for increased susceptibility to ileus and for the increased severity and duration of ileus observed in the elderly.     

IFN-alpha is not sufficient to drive Th1 development due to lack of stable T-bet expression

During inflammatory immune responses, the innate cytokine IL-12 promotes CD4+ Th-1 development through the activation of the second messenger STAT4 and the subsequent expression of T-bet. In addition, type I IFN (IFN-alphabeta), secreted primarily during viral and intracellular bacterial infections, can promote STAT4 activation in human CD4+ T cells. However, the role of IFN-alphabeta in regulating Th1 development is controversial, and previous studies have suggested a species-specific pathway leading to Th1 development in human but not mouse CD4+ T cells. In this study, we found that although both IFN-alpha and IL-12 can promote STAT4 activation, IFN-alpha failed to promote Th1 commitment in human CD4+ T cells. The difference between these innate signaling pathways lies with the ability of IL-12 to promote sustained STAT4 tyrosine phosphorylation, which correlated with stable T-bet expression in committed Th1 cells. IFN-alpha did not promote Th1 development in human CD4+ T cells because of attenuated STAT4 phosphorylation, which was insufficient to induce stable expression of T-bet. Further, the defect in IFN-alpha-driven Th1 development was corrected by ectopic expression of T-bet within primary naive human CD4+ T cells. These results indicate that IL-12 remains unique in its ability to drive Th1 development in human CD4+ T cells and that IFN-alpha lacks this activity due to its inability to promote sustained T-bet expression.     

Phenology, distribution, and host specificity of Solenopsis invicta virus-1

Studies were conducted to examine the phenology, geographic distribution, and host specificity of the Solenopsis invicta virus-1 (SINV-1). Two genotypes examined, SINV-1 and -1A, exhibited similar seasonal prevalence patterns. Infection rates among colonies of S. invicta in Gainesville, Florida, were lowest from early winter (December) to early spring (April) increasing rapidly in late spring (May) and remaining high through August before declining again in the fall (September/October). Correlation analysis revealed a significant relationship between mean monthly temperature and SINV-1 (p<0.0005, r=0.82) and SINV-1A (p<0.0001, r=0.86) infection rates in S. invicta colonies. SINV-1 was widely distributed among S. invicta populations. The virus was detected in S. invicta from Argentina and from all U.S. states examined, with the exception of New Mexico. SINV-1 and -1A were also detected in other Solenopsis species. SINV-1 was detected in Solenopsis richteri and the S. invicta/richteri hybrid collected from northern Alabama and Solenopsis geminata from Florida. SINV-1A was detected in S. geminata and Solenopsis carolinensis in Florida and the S. invicta/richteri hybrid in Alabama. Of the 1989 arthropods collected from 6 pitfall trap experiments from Gainesville and Williston, Florida, none except S. invicta tested positive for SINV-1 or SINV-1A. SINV-1 did not appear to infect or replicate within Sf9 or Dm-2 cells in vitro. The number of SINV-1 genome copies did not significantly increase over the course of the experiment, nor were any cytopathic effects observed. Phylogenetic analyses of SINV-1/-1A nucleotide sequences indicated significant divergence between viruses collected from Argentina and the U.S.