Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy

Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases.     

Space use by two arboreal rodent species in a Neotropical cloud forest

Studying animal space use patterns can help increase our understating of ecological processes such as competition and community dynamics. To quantify space and habitat use in an isolated and patchy cloud forest community in Mexico, we evaluate the vertical stratification, home range and habitat selection of two arboreal rodents: Habromys schmidlyi and Reithrodontomys microdon. Using live-traps at ground level and different forest strata, we radio-equipped nine individuals of H. schmidlyi and seven of R. microdon, and evaluated fine-scale space use and broad-scale habitat selection between cloud forest and oak forest. We found an average home range of 0.24 ha for R. microdon males and 0.72 ha for females, with a preference for higher canopy in the cloud forest. For H. schmidlyi the home range was 0.83 ha for males and 0.29 ha for females, with a preference for the understory level in the cloud forest. Home range is three-dimensional for these rodents, so we estimate that on average, individuals of both species used eight trees in the time they were tracked. We characterised the vegetation at the trap sites, and used recursive partitioning to relate the presence of different plants with the probability of finding these two species and Peromyscus aztecus, a third rodent species also present in the area and considered in our analysis of habitat use. The highest probability of finding R. microdon (96%) was related to the presence of Brachythecium occidentale and Renauldia mexicana, while H. schmidlyi (95%) was found in close proximity to Fabronia ciliaris and Everniastrum. We highlight the importance of arboreal trapping in biodiversity assessments, and the role of arboreal rodents in maintaining tropical forest ecosystems. We suggest that these rodent species could avoid or reduce competition by using the vertical strata differentially, and that H. schmidlyi and R. microdon can be biological indicators for cloud forest management and conservation.     

Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord

Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.     

Diet composition of an invasive population of Lithobates catesbeianus (American Bullfrog) from Argentina

The American bullfrog Lithobates catesbeianus has been introduced around the world, with invasive populations reported from almost all South American countries. A population of this species was introduced in the Calingasta department of San Juan province, which is an arid environment in western Argentina. This work provides information on the dietary composition of an invasive population of L. catesbeianus, and compares the degree of dietary overlap between adults and juveniles. Stomach contents of 169 bullfrogs (82 adults and 87 juveniles) were analysed. Adults consumed 40 prey taxa and Hymenoptera (Insecta) was the most numerous prey item (41.8%), followed by Araneae (13.6%) and Aeglidae (13.4%). Juveniles consumed 29 prey taxa and Hymenoptera constituted the highest percentage in prey number (77.2%). The trophic overlap niche index at the same level shows a value of 0.64 overlap in dietary community between adults and juveniles of this bullfrog. Aeglidae was volumetrically the most important trophic item (25.4%), followed by Anura (25.02%). Our results showed that cannibalism in bullfrogs is more common than the consumption of native anurans, coinciding with that reported in other populations of introduced bullfrogs. The high similarity in the diets of both size classes and the association between the size of the predator and prey suggest that the impact caused by bullfrogs throughout their ontogeny is high and probably has an impact on their prey. Freshwater crabs are the main items in the diet of Lithobates catesbeianus in other introduced populations and are usually the most conspicuous at our study site. The crabs in freshwater ecosystems are part of the lowest trophic level in the food chain. The major threats to the southern region’s freshwater crabs include deforestation, farming and exotic species. Lithobates catesbeianus has a generalist diet and high overlap between adults and juveniles.     

Year-round activity patterns in a hyperdiverse community of rainforest amphibians in Madagascar

Madagascar hosts a high diversity of amphibians estimated at over 500 species, nearly all of them endemic. Surprisingly few data are available on the activity cycles of this fauna, despite its importance for ecological, evolutionary and conservation research. Here we report the results of a year-round survey of amphibians along a transect bordering the Analamazaotra forest near Andasibe in central eastern Madagascar. During 120 transect walks evenly spaced through the year, a total of 2530 individuals of 40 species of anurans was observed. Abundance was higher during the warm/rainy season (December to April) and peaked in February. Of the five climatic predictors measured, only mean temperature and relative humidity showed high importance values, and multi-model averages indicate that these two variables have a strong effect on amphibian abundance along the transect. Species richness showed no evident peak during the study period and was best explained by a model including average temperature and rainfall. Canonical correspondence analysis indicates that Boophis sibilans, B. tephraeomystax, B. boehmei and Plethodontohyla notosticta were more frequently encountered along the transect on cold and humid days while Plethodontohyla mihanika, Gephyromantis boulengeri and Spinomantis aglavei were distinctly more abundant on cold and dry days, and Paradoxophyla palmata on warm and dry days. The results of our study flag a number of species as suitable candidates for future monitoring initiatives and suggest that a simple combination of visual and acoustic surveys can estimate amphibian activity with high sample sizes in Madagascar’s rainforests.     

Unobserved components in ARCH models: An application to seasonal adjustment

The paper deals with unobserved components in ARIMA models with GARCH errors, in the context of an actual application, namely seasonal adjustment of the monthly Spanish money supply series. The series shows clear evidence of (moderate) non-linearity, which does not disappear with simple outlier correction. The GARCH structure explains reasonably well the non-linearity, and this explanation is robust with respect to the GARCH specification. We look at the time variation of the standard error of the adjusted series estimator and show how it can be measured. Next, we look at the implications this variation has on short-term monetary control. The non-linearity seems to have a small effect in practice. It is further seen that the conditional variance of the GARCH process may, in turn, be decomposed into components. In fact, the conditional variance of the money supply series is the sum of a weak linear trend, a strong non-linear seasonal component, and a moderate non-linear irregular component. This information has policy implications: for example, there are periods in the year when policy can be more assertive because information is more precise. Finally, looking at the non-linear components of the money supply it is seen how linear combinations of non-linear series can produce series that behave linearly.     

Activation of ataxia telangiectasia muted under experimental models and human Parkinson’s disease

In the present study we demonstrated that neurotoxin MPP⁺-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP⁺-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson’s disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G₀/G₁ cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP⁺ leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP⁺ and cell-cycle re-entry through retinoblastoma protein phosphorylation.