Biodiversity and carbon (C) cycling have been the focus of much research in recent decades, partly because both change as a result of anthropogenic activities that are likely to continue. Soils are ...extremely species-rich and store approximately 80% of global terrestrial C. Soil organisms play a key role in C dynamics and a loss of species through global changes could influence global C dynamics. Here, we synthesize findings from published studies that have manipulated soil species richness and measured the response in terms of ecosystem functions related to C cycling (such as decomposition, respiration and the abundance or biomass of decomposer biota) to evaluate the impact of biodiversity loss on C dynamics. We grouped studies where one or more biotic groups had been manipulated to include a richness of ≤10 species or >10 species in order to reflect ‘low' and ‘high' extents of diversity manipulations. There was a positive relationship between species richness and C cycling in 77-100% of low-diversity experiments, even when the richness of just one biotic group was manipulated, whereas positive relationships occurred less frequently in studies with greater richness (35-64%). Moreover, when positive relationships were observed, these often indicated functional redundancy at low extents of diversity or that community composition had a stronger influence on C cycling than did species richness. Initial reductions in soil species richness resulting from global changes are unlikely to alter C dynamics significantly unless particularly influential species are lost. However, changes in community composition, and the loss of species with an ability to facilitate specialized soil processes related to C cycling, as a result of global changes, may have larger impacts on C dynamics.
Nucleotide changes in the AUTS2 locus, some of which affect only noncoding regions, are associated with autism and other neurological disorders, including attention deficit hyperactivity disorder, ...epilepsy, dyslexia, motor delay, language delay, visual impairment, microcephaly, and alcohol consumption. In addition, AUTS2 contains the most significantly accelerated genomic region differentiating humans from Neanderthals, which is primarily composed of noncoding variants. However, the function and regulation of this gene remain largely unknown. To characterize auts2 function, we knocked it down in zebrafish, leading to a smaller head size, neuronal reduction, and decreased mobility. To characterize AUTS2 regulatory elements, we tested sequences for enhancer activity in zebrafish and mice. We identified 23 functional zebrafish enhancers, 10 of which were active in the brain. Our mouse enhancer assays characterized three mouse brain enhancers that overlap an ASD-associated deletion and four mouse enhancers that reside in regions implicated in human evolution, two of which are active in the brain. Combined, our results show that AUTS2 is important for neurodevelopment and expose candidate enhancer sequences in which nucleotide variation could lead to neurological disease and human-specific traits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Genetic Basis for Bacterial Mercury Methylation Parks, Jerry M.; Johs, Alexander; Podar, Mircea ...
Science (American Association for the Advancement of Science),
03/2013, Letnik:
339, Številka:
6125
Journal Article
Recenzirano
Methylmercury is a potent neurotoxin produced in natural environments from inorganic mercury by anaerobic bacteria. However, until now the genes and proteins involved have remained unidentified. ...Here, we report a two-gene cluster, hgcA and hgcB, required for mercury methylation by Desulfovibrio desulfuricans ND132 and Geobacter sulfurreducens PCA. In either bacterium, deletion of hgcA, hgcB, or both genes abolishes mercury methylation. The genes encode a putative corrinoid protein, HgcA, and a 24Fe-4S ferredoxin, HgcB, consistent with roles as a methyl carrier and an electron donor required for corrinoid cofactor reduction, respectively. Among bacteria and archaea with sequenced genomes, gene orthologs are present in confirmed methylators but absent in nonmethylators, suggesting a common mercury methylation pathway in all methylating bacteria and archaea sequenced to date.
Recent human-genetics studies have come to different conclusions regarding how and when modern humans spread out of Africa and into the rest of the world. I present here a simple parsimony-based ...analysis that suggests that East Asians and Melanesians are sister groups, and I discuss what implications this has for recent claims made about the demographic histories of non-African populations.
Although autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) continue to rise in prevalence, together affecting >10% of today's pediatric population, the methods of ...diagnosis remain subjective, cumbersome and time intensive. With gaps upward of a year between initial suspicion and diagnosis, valuable time where treatments and behavioral interventions could be applied is lost as these disorders remain undetected. Methods to quickly and accurately assess risk for these, and other, developmental disorders are necessary to streamline the process of diagnosis and provide families access to much-needed therapies sooner. Using forward feature selection, as well as undersampling and 10-fold cross-validation, we trained and tested six machine learning models on complete 65-item Social Responsiveness Scale score sheets from 2925 individuals with either ASD (n=2775) or ADHD (n=150). We found that five of the 65 behaviors measured by this screening tool were sufficient to distinguish ASD from ADHD with high accuracy (area under the curve=0.965). These results support the hypotheses that (1) machine learning can be used to discern between autism and ADHD with high accuracy and (2) this distinction can be made using a small number of commonly measured behaviors. Our findings show promise for use as an electronically administered, caregiver-directed resource for preliminary risk evaluation and/or pre-clinical screening and triage that could help to speed the diagnosis of these disorders.
The investigation of the interconnections between the molecular and genetic events that govern biological systems is essential if we are to understand the development of disease and design effective ...novel treatments. Microarray and next-generation sequencing technologies have the potential to provide this information. However, taking full advantage of these approaches requires that biological connections be made across large quantities of highly heterogeneous genomic datasets. Leveraging the increasingly huge quantities of genomic data in the public domain is fast becoming one of the key challenges in the research community today.
We have developed a novel data mining framework that enables researchers to use this growing collection of public high-throughput data to investigate any set of genes or proteins. The connectivity between molecular states across thousands of heterogeneous datasets from microarrays and other genomic platforms is determined through a combination of rank-based enrichment statistics, meta-analyses, and biomedical ontologies. We address data quality concerns through dataset replication and meta-analysis and ensure that the majority of the findings are derived using multiple lines of evidence. As an example of our strategy and the utility of this framework, we apply our data mining approach to explore the biology of brown fat within the context of the thousands of publicly available gene expression datasets.
Our work presents a practical strategy for organizing, mining, and correlating global collections of large-scale genomic data to explore normal and disease biology. Using a hypothesis-free approach, we demonstrate how a data-driven analysis across very large collections of genomic data can reveal novel discoveries and evidence to support existing hypothesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Uranium reduction Wall, Judy D; Krumholz, Lee R
Annual review of microbiology,
01/2006, Letnik:
60
Journal Article
Recenzirano
The dramatic decrease in solubility accompanying the reduction of U(VI) to U(IV), producing the insoluble mineral uraninite, has been viewed as a potential mechanism for sequestration of ...environmental uranium contamination. In the past 15 years, it has been firmly established that a variety of bacteria exhibit this reductive capacity. To obtain an understanding of the microbial metal metabolism, to develop a practical approach for the acceleration of in situ bioreduction, and to predict the long-term fate of environmental uranium, several aspects of the microbial process have been experimentally explored. This review briefly addresses the research to identify specific uranium reductases and their cellular location, competition between uranium and other electron acceptors, attempts to stimulate in situ reduction, and mechanisms of reoxidation of reduced uranium minerals.
Identification of correct protein–ligand binding poses is important in structure-based drug design and crucial for the evaluation of protein–ligand binding affinity. Protein–ligand coordinates are ...commonly obtained from crystallography experiments that provide a static model of an ensemble of conformations. Binding pose metadynamics (BPMD) is an enhanced sampling method that allows for an efficient assessment of ligand stability in solution. Ligand poses that are unstable under the bias of the metadynamics simulation are expected to be infrequently occupied in the energy landscape, thus making minimal contributions to the binding affinity. Here, the robustness of the method is studied using crystal structures with ligands known to be incorrectly modeled, as well as 63 structurally diverse crystal structures with ligand fit to electron density from the Twilight database. Results show that BPMD can successfully differentiate compounds whose binding pose is not supported by the electron density from those with well-defined electron density.
Thousands of pathogens are known to infect humans, but only a fraction are readily identifiable using current diagnostic methods. Microbial cell-free DNA sequencing offers the potential to ...non-invasively identify a wide range of infections throughout the body, but the challenges of clinical-grade metagenomic testing must be addressed. Here we describe the analytical and clinical validation of a next-generation sequencing test that identifies and quantifies microbial cell-free DNA in plasma from 1,250 clinically relevant bacteria, DNA viruses, fungi and eukaryotic parasites. Test accuracy, precision, bias and robustness to a number of metagenomics-specific challenges were determined using a panel of 13 microorganisms that model key determinants of performance in 358 contrived plasma samples, as well as 2,625 infections simulated in silico and 580 clinical study samples. The test showed 93.7% agreement with blood culture in a cohort of 350 patients with a sepsis alert and identified an independently adjudicated cause of the sepsis alert more often than all of the microbiological testing combined (169 aetiological determinations versus 132). Among the 166 samples adjudicated to have no sepsis aetiology identified by any of the tested methods, sequencing identified microbial cell-free DNA in 62, likely derived from commensal organisms and incidental findings unrelated to the sepsis alert. Analysis of the first 2,000 patient samples tested in the CLIA laboratory showed that more than 85% of results were delivered the day after sample receipt, with 53.7% of reports identifying one or more microorganisms.
Simulation of genomic sequences under the coalescent with recombination has conventionally been impractical for regions beyond tens of megabases. This work presents an algorithm, implemented as the ...program MaCS (Markovian Coalescent Simulator), that can efficiently simulate haplotypes under any arbitrary model of population history. We present several metrics comparing the performance of MaCS with other available simulation programs. Practical usage of MaCS is demonstrated through a comparison of measures of linkage disequilibrium between generated program output and real genotype data from populations considered to be structured.
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