Inflammation and Pyroptosis Mediate Muscle Expansion in an Interleukin-1β (IL-1β)-dependent Manner

Muscle inflammation is often associated with its expansion. Bladder smooth muscle inflammation-induced cell death is accompanied by hyperplasia and hypertrophy as the primary cause for poor bladder function. In mice, DNA damage initiated by chemotherapeutic drug cyclophosphamide activated caspase 1 through the formation of the NLRP3 complex resulting in detrusor hyperplasia. A cyclophosphamide metabolite, acrolein, caused global DNA methylation and accumulation of DNA damage in a mouse model of bladder inflammation and in cultured bladder muscle cells. In correlation, global DNA methylation and NLRP3 expression was up-regulated in human chronic bladder inflammatory tissues. The epigenetic silencing of DNA damage repair gene, Ogg1, could be reversed by the use of demethylating agents. In mice, demethylating agents reversed cyclophosphamide-induced bladder inflammation and detrusor expansion. The transgenic knock-out of Ogg1 in as few as 10% of the detrusor cells tripled the proliferation of the remaining wild type counterparts in an in vitro co-culture titration experiment. Antagonizing IL-1β with Anakinra, a rheumatoid arthritis therapeutic, prevented detrusor proliferation in conditioned media experiments as well as in a mouse model of bladder inflammation. Radiation treatment validated the role of DNA damage in the NLRP3-associated caspase 1-mediated IL-1β secretory phenotype. A protein array analysis identified IGF1 to be downstream of IL-1β signaling. IL-1β-induced detrusor proliferation and hypertrophy could be reversed with the use of Anakinra as well as an IGF1 neutralizing antibody. IL-1β antagonists in current clinical practice can exploit the revealed mechanism for DNA damage-mediated muscular expansion.     

A Generalized Deforestation and Land-Use Change Scenario Generator for Use in Climate Modelling Studies

A new deforestation and land-use change scenario generator model (FOREST-SAGE) is presented that is designed to interface directly with dynamic vegetation models used in latest generation earth system models. The model requires a regional-scale scenario for aggregate land-use change that may be time-dependent, provided by observational studies or by regional land-use change/economic models for future projections. These land-use categories of the observations/economic model are first translated into equivalent plant function types used by the particular vegetation model, and then FOREST-SAGE disaggregates the regional-scale scenario to the local grid-scale of the earth system model using a set of risk-rules based on factors such as proximity to transport networks, distance weighted population density, forest fragmentation and presence of protected areas and logging concessions. These rules presently focus on the conversion of forest to agriculture and pasture use, but could be generalized to other land use change conversions. After introducing the model, an evaluation of its performance is shown for the land-cover changes that have occurred in the Central African Basin from 2001–2010 using retrievals from MODerate Resolution Imaging Spectroradiometer Vegetation Continuous Field data. The model is able to broadly reproduce the spatial patterns of forest cover change observed by MODIS, and the use of the local-scale risk factors enables FOREST-SAGE to improve land use change patterns considerably relative to benchmark scenarios used in the latest Coupled Model Intercomparison Project integrations. The uncertainty to the various risk factors is investigated using an ensemble of investigations, and it is shown that the model is sensitive to the population density, forest fragmentation and reforestation factors specified.     

The Paternal Landscape along the Bight of Benin – Testing Regional Representativeness of West-African Population Samples Using Y-Chromosomal Markers

Patterns of genetic variation in human populations across the African continent are still not well studied in comparison with Eurasia and America, despite the high genetic and cultural diversity among African populations. In population and forensic genetic studies a single sample is often used to represent a complete African region. In such a scenario, inappropriate sampling strategies and/or the use of local, isolated populations may bias interpretations and pose questions of representativeness at a macrogeographic-scale. The non-recombining region of the Y-chromosome (NRY) has great potential to reveal the regional representation of a sample due to its powerful phylogeographic information content. An area poorly characterized for Y-chromosomal data is the West-African region along the Bight of Benin, despite its important history in the trans-Atlantic slave trade and its large number of ethnic groups, languages and lifestyles. In this study, Y-chromosomal haplotypes from four Beninese populations were determined and a global meta-analysis with available Y-SNP and Y-STR data from populations along the Bight of Benin and surrounding areas was performed. A thorough methodology was developed allowing comparison of population samples using Y-chromosomal lineage data based on different Y-SNP panels and phylogenies. Geographic proximity turned out to be the best predictor of genetic affinity between populations along the Bight of Benin. Nevertheless, based on Y-chromosomal data from the literature two population samples differed strongly from others from the same or neighbouring areas and are not regionally representative within large-scale studies. Furthermore, the analysis of the HapMap sample YRI of a Yoruban population from South-western Nigeria based on Y-SNPs and Y-STR data showed for the first time its regional representativeness, a result which is important for standard population and forensic genetic applications using the YRI sample. Therefore, the uniquely and powerful geographical information carried by the Y-chromosome makes it an important locus to test the representativeness of a certain sample even in the genomic era, especially in poorly investigated areas like Africa.     

The noncoding RNA CcnA modulates the master cell cycle regulators CtrA and GcrA in Caulobacter crescentus

Bacteria are powerful models for understanding how cells divide and accomplish global regulatory programs. In Caulobacter crescentus, a cascade of essential master regulators supervises the correct and sequential activation of DNA replication, cell division, and development of different cell types. Among them, the response regulator CtrA plays a crucial role coordinating all those functions. Here, for the first time, we describe the role of a novel factor named CcnA (cell cycle noncoding RNA A), a cell cycle–regulated noncoding RNA (ncRNA) located at the origin of replication, presumably activated by CtrA, and responsible for the accumulation of CtrA itself. In addition, CcnA may be also involved in the inhibition of translation of the S-phase regulator, GcrA, by interacting with its 5′ untranslated region (5′ UTR). Performing in vitro experiments and mutagenesis, we propose a mechanism of action of CcnA based on liberation (ctrA) or sequestration (gcrA) of their ribosome-binding site (RBS). Finally, its role may be conserved in other alphaproteobacterial species, such as Sinorhizobium meliloti, representing indeed a potentially conserved process modulating cell cycle in Caulobacterales and Rhizobiales.

During cell cycle progression in the bacterium Caulobacter crescentus, the master cell cycle regulator CtrA is controlled by CcnA, a cell cycle-regulated non-coding RNA transcribed from a gene located at the origin of replication.     

Genetic population structure of two African-Ecuadorian communities of Esmeraldas

The genetic structure of two African-Ecuadorian communities, Rio Cayapas and Viche (Esmeraldas province, northwest Ecuador), was studied on the basis of ACP1, ADA, AK1, CA2, ESD, GLO1, G6PD, PGD, and PGM1 subtypes and thermostability, PGM2, HBβ, F13A, F13B, ORM1, AHSG, C6, C7, and APOC2 gene frequency, and migration data on 255 individuals. The fixation index of Wright (F_ST), correspondence, and genetic distance analysis were applied to compare the genetic relationships between these communities and other American populations of African ancestry. F_ST values from the migration data and surname origins suggest that Rio Cayapas is genetically more isolated and shows less mobility and admixture than does Viche. The genetic admixture estimates indicate a large contribution of African genes to the gene pool of both communities (74.3% to 58.4%), whereas the proportion of the Amerindian component differs significantly (14.5% in Rio Cayapas to 27.6% in Viche). Am J Phys Anthropol 109:159–174, 1999.© 1999 Wiley-Liss, Inc.     

Worldclim 2.1 versus Worldclim 1.4: Climatic niche and grid resolution affect between‐version mismatches in Habitat Suitability Models predictions across Europe

The influence of climate on the distribution of taxa has been extensively investigated in the last two decades through Habitat Suitability Models (HSMs). In this context, the Worldclim database represents an invaluable data source as it provides worldwide climate surfaces for both historical and future time horizons. Thousands of HSMs‐based papers have been published taking advantage of Worldclim 1.4, the first online version of this repository. In 2017, Worldclim 2.1 was released. Here, we evaluated spatially explicit prediction mismatch at continental scale, focusing on Europe, between HSMs fitted using climate surfaces from the two Worldclim versions (between‐version differences). To this aim, we simulated occurrence probability and presence‐absence across Europe of four virtual species (VS) with differing climate‐occurrence relationships. For each VS, we fitted HSMs upon uncorrelated bioclimatic variables derived from each Worldclim version at three grid resolutions. For each factor combination, HSMs attaining sufficient discrimination performance on spatially independent test data were projected across Europe under current conditions and various future scenarios, and importance scores of the single variables were computed. HSMs failed in accurately retrieving the simulated climate‐occurrence relationships for the climate‐tolerant VS and the one occurring under a narrow combination of climatic conditions. Under current climate, noticeable between‐version prediction mismatch emerged across most of Europe for these two VSs, whose simulated suitability mainly depended upon diurnal or yearly variability in temperature; differently, between‐version differences were more clustered toward areas showing extreme values, like mountainous massifs or southern regions, for VSs responding to average temperature and precipitation trends. Under future climate, the chosen emission scenarios and Global Climate Models did not evidently influence between‐version prediction discrepancies, while grid resolution synergistically interacted with VSs'' niche characteristics in determining extent of such differences. Our findings could help in re‐evaluating previous biodiversity‐related works relying on geographical predictions from Worldclim‐based HSMs.     

Demographic and spatial analysis of a population of Juniperus oxycedrus L. in an abandoned grassland

A study of the structural, dynamic, and space occupancy characteristics of a prickly juniper (Juniperus oxycedrus) population developed on an abandoned secondary grassland of the Central Apennines (Italy), is presented here. The data were collected from a permanent plot, limited by mixed deciduous woods dominated by Ostrya carpinifolia Scop. by a plantation of Pinus nigra Arnold, and by a forest road, and consisting of 1744 prickly juniper individuals, as well as other pre-forest and forest species. The age and sex distributions of this population were assessed. With these data, the age pyramid was constructed, within which three developmental phases of the population became apparent, as confirmed by a study of the logistic curve of development of the population. Based on an estimate of the intensity function of the spatial distribution of the prickly juniper individuals, the hypothesis of complete randomness has to be rejected. On the other hand, the correlation between sex and population density was significant. The mode of space occupancy of the prickly juniper population was investigated also with respect to the other populations of shrubs and forest species. It was shown to spread out in all directions, following lines of diffusion that could be randomly determined. Finally, the presence, within the plot, of some pasture areas not occupied by prickly juniper may be derived from lack of germination of the fruits, or development of the seedlings owing to unfavourable micro-environmental conditions.