Potent effect of target structure on microRNA function

MicroRNAs (miRNAs) are small noncoding RNAs that repress protein synthesis by binding to target messenger RNAs. We investigated the effect of target secondary structure on the efficacy of repression by miRNAs. Using structures predicted by the Sfold program, we model the interaction between an miRNA and a target as a two-step hybridization reaction: nucleation at an accessible target site followed by hybrid elongation to disrupt local target secondary structure and form the complete miRNA-target duplex. This model accurately accounts for the sensitivity to repression by let-7 of various mutant forms of the Caenorhabditis elegans lin-41 3' untranslated region and for other experimentally tested miRNA-target interactions in C. elegans and Drosophila melanogaster. These findings indicate a potent effect of target structure on target recognition by miRNAs and establish a structure-based framework for genome-wide identification of animal miRNA targets.     

Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model

Background

Availability of an ultra-short-course drug regimen capable of curing patients with tuberculosis in 2 to 3 mo would significantly improve global control efforts. Because immediate prospects for novel treatment-shortening drugs remain uncertain, we examined whether better use of existing drugs could shorten the duration of treatment. Rifapentine is a long-lived rifamycin derivative currently recommended only in once-weekly continuation-phase regimens. Moxifloxacin is an 8-methoxyfluoroquinolone currently used in second-line regimens.

Methods and Findings

Using a well-established mouse model with a high bacterial burden and human-equivalent drug dosing, we compared the efficacy of rifapentine- and moxifloxacin-containing regimens with that of the standard daily short-course regimen based on rifampin, isoniazid, and pyrazinamide. Bactericidal activity was assessed by lung colony-forming unit counts, and sterilizing activity was assessed by the proportion of mice with culture-positive relapse after 2, 3, 4, and 6 mo of treatment. Here, we demonstrate that replacing rifampin with rifapentine and isoniazid with moxifloxacin dramatically increased the activity of the standard daily regimen. After just 2 mo of treatment, mice receiving rifapentine- and moxifloxacin-containing regimens were found to have negative lung cultures, while those given the standard regimen still harbored 3.17 log₁₀ colony-forming units in the lungs (p < 0.01). No relapse was observed after just 3 mo of treatment with daily and thrice-weekly administered rifapentine- and moxifloxacin-containing regimens, whereas the standard daily regimen required 6 mo to prevent relapse in all mice.

Conclusions

Rifapentine should no longer be viewed solely as a rifamycin for once-weekly administration. Our results suggest that treatment regimens based on daily and thrice-weekly administration of rifapentine and moxifloxacin may permit shortening the current 6 mo duration of treatment to 3 mo or less. Such regimens warrant urgent clinical investigation.     

Spatial distribution and landscape associations of large-antlered deer

For more than a century, the Boone and Crockett Club has kept records of harvest locations for 38 categories of North American big game, which includes measurement details and sizes of enduring characteristics (e.g., antlers, skulls, horns). All white-tailed deer (Odocoileus virginianus) entered in the Club records (i.e., record deer) have large antlers because the measurements must meet or exceed a minimum size to qualify for entry. We used the records from the Club to test the hypothesis that the spatial distribution in the harvest of record deer was related to the number of antlered deer harvested, variations in land productivity, soil mineral content, and attributes of land cover for 9 states in the midwestern United States. We used a Bayesian theoretical framework to develop a spatial model that examined the influence of explanatory variables on the number of record deer harvested in each county. In our study area, 3,658 record deer were harvested in 692 of the 856 counties (80.8%). More record deer were harvested in counties that had more high-contrast edges, less contiguous land cover, and greater variation in soil productivity. These results provide information for managers and hunters to better understand the spatial distribution of record deer and factors that are correlated with their distribution. © 2019 The Wildlife Society.     

Water availability shapes edaphic and lithic cyanobacterial communities in the Atacama Desert

In the Atacama Desert, cyanobacteria grow on various substrates such as soils (edaphic) and quartz or granitoid stones (lithic). Both edaphic and lithic cyanobacterial communities have been described but no comparison between both communities of the same locality has yet been undertaken. In the present study, we compared both cyanobacterial communities along a precipitation gradient ranging from the arid National Park Pan de Azúcar (PA), which resembles a large fog oasis in the Atacama Desert extending to the semiarid Santa Gracia Natural Reserve (SG) further south, as well as along a precipitation gradient within PA. Various microscopic techniques, as well as culturing and partial 16S rRNA sequencing, were applied to identify 21 cyanobacterial species; the diversity was found to decline as precipitation levels decreased. Additionally, under increasing xeric stress, lithic community species composition showed higher divergence from the surrounding edaphic community, resulting in indigenous hypolithic and chasmoendolithic cyanobacterial communities. We conclude that rain and fog water, respectively, cause contrasting trends regarding cyanobacterial species richness in the edaphic and lithic microhabitats.     

High-resolution imaging of rhizosphere oxygen (O2) dynamics in Potamogeton crispus: effects of light,temperature and O2 content in overlying water

Plant and Soil - Radial oxygen loss (ROL) for macrophytes is intimately involved in their survival and growth, thus detailed characterizations of ROL and its implication for geochemical processes...     

Higher-Order Thalamocortical Inputs Gate Synaptic Long-Term Potentiation via Disinhibition

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