Agouti reintroduction recovers seed dispersal of a large-seeded tropical tree

The aim of animal reintroductions has mainly been species recovery; only few reintroduction initiatives focus on ecosystem restoration. Therefore, reintroduction consequences on ecological interactions are seldom assessed. We used the interaction between a reintroduced population of agoutis (Dasyprocta leporina) and a vulnerable tropical endemic tree (Joannesia princeps) to examine reintroduction effects on seed dispersal and seedling establishment. To test the outcomes of this interaction, we tracked seeds of J. princeps in two adjacent forest areas with and without reintroduced agoutis. We also assessed if dispersal distances affected seedling survival. To determine seed fate and dispersal distance, we used spool-and-line tracking, together with camera traps to identify dispersers. Agoutis were the only species removing J. princeps seeds, thus dispersal only occurred where agoutis had been reintroduced; in the area without agoutis, all seeds remained intact on the soil, even one year after the experiment's beginning. At the reintroduction area, most seeds were preyed upon by agoutis but 7% remained dispersed and 2% germinated after ten months. Only seeds buried by agoutis were able to germinate. Most dispersed seeds were dispersed 15 m or farther and longer dispersal distances benefited J. princeps, since seedlings farther from a conspecific adult tree had greater survival probability. Agoutis were also seen burying seeds of two other plant species; these mammals have the potential to benefit dozens of large-seeded species in our study system. Agouti reintroduction thus exemplifies the value of trophic rewilding programs to re-establish ecological interactions and restore ecosystem functioning.     

Disease swamps molecular signatures of genetic-environmental associations to abiotic factors in Tasmanian devil (Sarcophilus harrisii) populations

Landscape genomics studies focus on identifying candidate genes under selection via spatial variation in abiotic environmental variables, but rarely by biotic factors (i.e., disease). The Tasmanian devil (Sarcophilus harrisii) is found only on the environmentally heterogeneous island of Tasmania and is threatened with extinction by a transmissible cancer, devil facial tumor disease (DFTD). Devils persist in regions of long-term infection despite epidemiological model predictions of species’ extinction, suggesting possible adaptation to DFTD. Here, we test the extent to which spatial variation and genetic diversity are associated with the abiotic environment (i.e., climatic variables, elevation, vegetation cover) and/or DFTD. We employ genetic-environment association analyses using 6886 SNPs from 3287 individuals sampled pre- and post-disease arrival across the devil's geographic range. Pre-disease, we find significant correlations of allele frequencies with environmental variables, including 365 unique loci linked to 71 genes, suggesting local adaptation to abiotic environment. The majority of candidate loci detected pre-DFTD are not detected post-DFTD arrival. Several post-DFTD candidate loci are associated with disease prevalence and were in linkage disequilibrium with genes involved in tumor suppression and immune response. Loss of apparent signal of abiotic local adaptation post-disease suggests swamping by strong selection resulting from the rapid onset of DFTD.     

Leading compounds for the validation of animal models of psychopathology

Modelling of complex psychiatric disorders, e.g., depression and schizophrenia, in animals is a major challenge, since they are characterized by certain disturbances in functions that are absolutely unique to humans. Furthermore, we still have not identified the genetic and neurobiological mechanisms, nor do we know precisely the circuits in the brain that function abnormally in mood and psychotic disorders. Consequently, the pharmacological treatments used are mostly variations on a theme that was started more than 50 years ago. Thus, progress in novel drug development with improved therapeutic efficacy would benefit greatly from improved animal models. Here, we review the available animal models of depression and schizophrenia and focus on the way that they respond to various types of potential candidate molecules, such as novel antidepressant or antipsychotic drugs, as an index of predictive validity. We conclude that the generation of convincing and useful animal models of mental illnesses could be a bridge to success in drug discovery.     

MMP-2 −1306C > T polymorphism in breast cancer: a case–control study in a South European population

This case control study aims to investigate the role of MMP-2 ?1306C > T polymorphism as a potential risk factor and possible prognostic marker for breast cancer in a South European population. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. MMP-2 ?1306C > T polymorphism was genotyped; multivariate logistic regression as well as Cox regression analysis were performed. MMP-2 ?1306C > T status was not associated with breast cancer risk either at the total sample or at the subanalyses on premenopausal and postmenopausal women. At the survival analysis, a trend towards a favorable association between MMP-2 ?1306C > T allele and disease-free survival as well as overall survival was observed. Regarding subanalyses on ER-negative and ER-positive cases, the favorable association implicating MMP-2 ?1306C > T allele was particularly evident among ER-positive cases; no significant associations emerged among ER-negative cases. MMP-2 ?1306C > T polymorphism does not seem to be a risk factor for breast cancer in South European population; however, a trend towards a favorable association with survival has been observed.     

Delivery and processing of exogenous double-stranded DNA in mouse CD34 + hematopoietic progenitor cells and their cell cycle changes upon combined treatment with cyclophosphamide and double-stranded DNA

We previously reported that fragments of exogenous double-stranded DNA can be internalized by mouse bone marrow cells without any transfection. Our present analysis shows that only 2% of bone marrow cells take up the fragments of extracellular exogenous DNA. Of these, ~ 45% of the cells correspond to CD34 + hematopoietic stem cells. Taking into account that CD34 + stem cells constituted 2.5% of the total cell population in the bone marrow samples analyzed, these data indicate that as much as 40% of CD34 + cells readily internalize fragments of extracellular exogenous DNA. This suggests that internalization of fragmented dsDNA is a general feature of poorly differentiated cells, in particular CD34 + bone marrow cells.     

Compensatory nature of Chargaff’s second parity rule

The second parity rule of Chargaff (A≈T and G≈C within one strand) holds all over the living world with minor exceptions. It is maintained with higher accuracy for long sequences. The question addressed in the article is how different sequence types, with different biases from the parity, contribute to the general effect. It appears that the sequence segments with biases of opposite sign are intermingled, so that with sufficient sequence lengths the parity is established. The parity rule seems to be a cumulative result of a number of independent processes in the genome evolution, with the parity as their intrinsic property. Symmetrical appearance of simple repeats and of Alu sequences in the human DNA strands, and other contributions to the Chargaff parity II rule are discussed.     

CD4+ T Cells Support Production of Simian Immunodeficiency Virus Env Antibodies That Enforce CD4-Dependent Entry and Shape Tropism In Vivo

CD4⁺ T cells rather than macrophages are the principal cells infected by human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) in vivo. Macrophage tropism has been linked to the ability to enter cells through CCR5 in conjunction with limiting CD4 levels, which are much lower on macrophages than on T cells. We recently reported that rhesus macaques (RM) experimentally depleted of CD4⁺ T cells before SIV infection exhibit extensive macrophage infection as well as high chronic viral loads and rapid progression to AIDS. Here we show that early-time-point and control Envs were strictly CD4 dependent but that, by day 42 postinfection, plasma virus of CD4⁺ T cell-depleted RM was dominated by Envs that mediate efficient infection using RM CCR5 independently of CD4. Early-time-point and control RM Envs were resistant to neutralization by SIV-positive (SIV⁺) plasma but became sensitive if preincubated with sCD4. In contrast, CD4-independent Envs were highly sensitive to SIV⁺ plasma neutralization. However, plasma from SIV-infected CD4⁺ T cell-depleted animals lacked this CD4-inducible neutralizing activity and failed to neutralize any Envs regardless of sCD4 pre-exposure status. Enhanced sensitivity of CD4-independent Envs from day 42 CD4⁺ T cell-depleted RM was also seen with monoclonal antibodies that target both known CD4-inducible and other Env epitopes. CD4 independence and neutralization sensitivity were both conferred by Env amino acid changes E84K and D470N that arose independently in multiple animals, with the latter introducing a potential N-linked glycosylation site within a predicted CD4-binding pocket of gp120. Thus, the absence of CD4 T cells results in failure to produce antibodies that neutralize CD4-independent Envs and CD4-pretriggered control Envs. In the absence of this constraint and with a relative paucity of CD4⁺ target cells, widespread macrophage infection occurs in vivo accompanied by emergence of variants carrying structural changes that enable entry independently of CD4.