The influence of environment,sex, and innate timing mechanisms on body temperature patterns of free-ranging black-tailed prairie dogs (Cynomys ludovicianus)

Mechanisms that influence body temperature patterns in black-tailed prairie dogs are not well understood. Previous research on both free-ranging and laboratory populations of black-tailed prairie dogs (Cynomys ludovicianus) has suggested that reductions in ambient temperature and food and water deprivation are the primary factors that stimulate torpor in this species. In other species, however, torpor has been shown to be influenced by a multitude of factors, including innate circadian and circannual timing mechanisms, energy status, and reproductive behaviors. Our objective was to clarify the influence of weather, sex, and intrinsic timing mechanisms on the body temperature patterns of free-ranging black-tailed prairie dogs. We monitored body temperatures of eight adult (>1 yr) prairie dogs from November 1999 to June 2000. Prairie dogs showed distinct daily and seasonal body temperature patterns, which reflected changes in ambient temperatures that occurred during these periods. These patterns of daily and seasonal heterothermy suggest that body temperature patterns of black-tailed prairie dogs may be driven by an innate timing mechanism. All prairie dogs entered torpor intermittently throughout winter and spring. Torpor bouts appeared to be influenced by precipitation and reductions in ambient temperature. Our results also suggest that reproductive behaviors and circadian timing may influence torpor in this species.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.     

Mesenchymal stem cells in autoimmune diseases: hype or hope?

Intervention with mesenchymal stem cells (MSCs) represents a promising therapeutic tool in treatment-refractory autoimmune diseases. A new report by Schurgers and colleagues in a previous issue of Arthritis Research & Therapy sheds novel mechanistic insight into the pathways employed by MSCs to suppress T-cell proliferation in vitro, but, at the same time, indicates that MSCs do not influence T-cell reactivity and the disease course in an in vivo arthritis model. Such discrepancies between the in vitro and in vivo effects of potent cellular immune modulators should spark further research and should be interpreted as a sign of caution for the in vitro design of MSC-derived interventions in the setting of human autoimmune diseases.     

Differential resource allocation in deer mice exposed to sin nombre virus

The resource allocation hypothesis predicts that reproductive activity suppresses immunocompetence; however, this has never been tested in an endemic disease system with free-ranging mammals. We tested the resource allocation hypothesis in wild deer mice (Peromyscus maniculatus) with natural exposure to Sin Nombre Virus (SNV). Immunocompetence was estimated from the extent of swelling elicited after deer mice were injected with phytohemagglutinin (PHA); swelling is positively correlated with immunocompetence. After livetrapping deer mice, we determined their reproductive state and SNV infection status. Males were more likely to be seropositive for SNV than females (37% vs. 25%) and exhibited 10% less swelling after PHA injection. The swelling response of females differed with both infection status and reproductive condition. There was also a significant infection status by reproductive condition interaction: non-reproductive, seropositive females experienced the least amount of swelling, whereas females in all other categories experienced significantly greater swelling. The swelling response of males differed with both SNV infection status and reproductive condition, but there was no significant infection status by reproductive condition interaction. Seronegative males elicited greater swelling than seropositive males regardless of reproductive status. In contrast to the resource allocation hypothesis, these results do not indicate that reproductive activity suppresses immunocompetence of deer mice but rather suggest that chronic SNV infection reduces immunocompetence. Sex-based differences in swelling indicate that SNV modulates the immune system of female deer mice differently than it does that of males, particularly during reproduction. We propose that differences in resource allocation between males and females could result from inherent sex-based differences in parental investment.     

Pentacycloundecane lactam vs lactone norstatine type protease HIV inhibitors: binding energy calculations and DFT study

Background

Novel pentacycloundecane (PCU)-lactone-CO-EAIS peptide inhibitors were designed, synthesized, and evaluated against wild-type C-South African (C-SA) HIV-1 protease. Three compounds are reported herein, two of which displayed IC₅₀ values of less than 1.00 μM. A comparative MM-PB(GB)SA binding free energy of solvation values of PCU-lactam and lactone models and their enantiomers as well as the PCU-lactam-NH-EAIS and lactone-CO-EAIS peptide inhibitors and their corresponding diastereomers complexed with South African HIV protease (C-SA) was performed. This will enable us to rationalize the considerable difference between inhibitory concentration (IC₅₀) of PCU-lactam-NH-EAIS and PCU-lactone-CO-EAIS peptides.

Results

The PCU-lactam model exhibited more negative calculated binding free energies of solvation than the PCU-lactone model. The same trend was observed for the PCU-peptide inhibitors, which correspond to the experimental activities for the PCU-lactam-NH-EAIS peptide (IC₅₀ = 0.076 μM) and the PCU-lactone-CO-EAIS peptide inhibitors (IC₅₀ = 0.850 μM). Furthermore, a density functional theory (DFT) study on the natural atomic charges of the nitrogen and oxygen atoms of the three PCU-lactam, PCU-lactim and PCU-lactone models were performed using natural bond orbital (NBO) analysis. Electrostatic potential maps were also used to visualize the electron density around electron-rich regions. The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory. Electronic molecular properties including polarizability and electric dipole moments were also calculated and compared. The Gibbs theoretical free solvation energies of solvation (∆G_solv) were also considered.

Conclusions

A general trend is observed that the lactam species appears to have a larger negative charge distribution around the heteroatoms, larger quadrupole constant, dipole moment and better solvation energy, in comparison to the PCU-lactone model. It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental IC₅₀ data.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-015-0115-5) contains supplementary material, which is available to authorized users.     

Loss of CDK5RAP2 affects neural but not non-neural mESC differentiation into cardiomyocytes

Biallelic mutations in the gene encoding centrosomal CDK5RAP2 lead to autosomal recessive primary microcephaly (MCPH), a disorder characterized by pronounced reduction in volume of otherwise architectonical normal brains and intellectual deficit. The current model for the microcephaly phenotype in MCPH invokes a premature shift from symmetric to asymmetric neural progenitor-cell divisions with a subsequent depletion of the progenitor pool. The isolated neural phenotype, despite the ubiquitous expression of CDK5RAP2, and reports of progressive microcephaly in individual MCPH cases prompted us to investigate neural and non-neural differentiation of Cdk5rap2-depleted and control murine embryonic stem cells (mESC). We demonstrate an accumulating proliferation defect of neurally differentiating Cdk5rap2-depleted mESC and cell death of proliferative and early postmitotic cells. A similar effect does not occur in non-neural differentiation into beating cardiomyocytes, which is in line with the lack of non-central nervous system features in MCPH patients. Our data suggest that MCPH is not only caused by premature differentiation of progenitors, but also by reduced propagation and survival of neural progenitors.     

RETRACTED ARTICLE: Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium

Introduction  

Mast cells have been implicated to play a functional role in arthritis, especially in autoantibody-positive disease. Among the cytokines involved in rheumatoid arthritis (RA), IL-17 is an important inflammatory mediator. Recent data suggest that the synovial mast cell is a main producer of IL-17, although T cells have also been implicated as prominent IL-17 producers as well. We aimed to identify IL-17 expression by mast cells and T cells in synovium of arthritis patients.     

The interplay of plant and animal disease in a changing landscape: the role of sudden aspen decline in moderating Sin Nombre virus prevalence in natural deer mouse populations

We examined how climate-mediated forest dieback regulates zoonotic disease prevalence using the relationship between sudden aspen decline (SAD) and Sin Nombre virus (SNV) as a model system. We compared understory plant community structure, small mammal community composition, and SNV prevalence on 12 study sites within aspen forests experiencing levels of SAD ranging from <10.0% crown fade to >95.0% crown fade. Our results show that sites with the highest levels of SAD had reduced canopy cover, stand density, and basal area, and these differences were reflected by reductions in understory vegetation cover. Conversely, sites with the highest levels of SAD had greater understory standing biomass, suggesting that vegetation on these sites was highly clustered. Changes in forest and understory vegetation structure likely resulted in shifts in small mammal community composition across the SAD gradient, as we found reduced species diversity and higher densities of deer mice, the primary host for SNV, on sites with the highest levels of SAD. Sites with the highest levels of SAD also had significantly greater SNV prevalence compared to sites with lower levels of SAD, which is likely a result of their abundance of deer mice. Collectively, results of our research provide strong evidence to show SAD has considerable impacts on vegetation community structure, small mammal density and biodiversity and the prevalence of SNV.     

Development of enzyme-immunoassays based on egg yolk antibodies for the detection of mycotoxins

Enzyme-linked immunosorbent assays (ELISA) proved to be a fast and simple method for the detection of mycotoxins and other undesired contaminants in food and feed. The present study is focused on the optimisation and exploitation of the egg yolk antibody technology in order to develop competitive ELISAs for the detection of mycotoxins in cereals. Due to its importance as one of the most relevant Fusarium mycotoxins, the trichothecene deoxynivalenol (DON) was selected as representative. Chickens were immunised with different protein conjugates performing varying booster intervals. The antibodies were isolated by the poly(ethylene glycol) precipitation method according to Polson. By use of these antibodies an indirect competitive ELISA was developed for the detection of DON. First investigations of naturally contaminated wheat samples showed a good correspondence with results obtained by GC-ECD when calibration in blank wheat extracts was performed.