Inactivation of the microRNA-183/96/182 cluster results in syndromic retinal degeneration

The microRNA-183/96/182 cluster is highly expressed in the retina and other sensory organs. To uncover its in vivo functions in the retina, we generated a knockout mouse model, designated “miR-183C(GT/GT),” using a gene-trap embryonic stem cell clone. We provide evidence that inactivation of the cluster results in early-onset and progressive synaptic defects of the photoreceptors, leading to abnormalities of scotopic and photopic electroretinograms with decreased b-wave amplitude as the primary defect and progressive retinal degeneration. In addition, inactivation of the miR-183/96/182 cluster resulted in global changes in retinal gene expression, with enrichment of genes important for synaptogenesis, synaptic transmission, photoreceptor morphogenesis, and phototransduction, suggesting that the miR-183/96/182 cluster plays important roles in postnatal functional differentiation and synaptic connectivity of photoreceptors

NANOG induction of fetal liver kinase-1 (FLK1) transcription regulates endothelial cell proliferation and angiogenesis

NANOG is a master transcription factor associated with the maintenance of stem cell pluripotency. Here, we demonstrate that transcription factor NANOG is expressed in cultured endothelial cells (ECs) and in a subset of tumor cell lines. Importantly, we provide evidence that WNT3A stimulation of ECs induces the transcription of NANOG which mediates the expression of vascular endothelial growth factor receptor-2, also known as fetal liver kinase-1 (FLK1). We defined ATTA as a minimal binding site for NANOG. Accordingly, a luciferase reporter assay showed that NANOG binds to and activates 4 ATTA binding sites identified in the FLK1 promoter after WNT3A stimulation. Consistent with this data, we found that, under basal conditions and in response to WNT3A stimulation, NANOG binding to these ATTA sequences markedly induced the expression of FLK1. Thus, our data indicate an essential role in angiogenesis for NANOG binding to these 4 ATTA sites. Surprisingly, NANOG depletion not only decreased FLK1 expression but also reduced cell proliferation and angiogenesis. These findings show the necessary and sufficient role of NANOG in inducing the transcription of FLK1 to regulate the angiogenic phenotypes of ECs

Genetic signatures indicate widespread antibiotic resistance and phage infection in microbial communities of the McMurdo Dry Valleys, East Antarctica

The McMurdo Dry Valleys of Antarctica support extensive yet cryptic microbial communities but little evidence for ‘top-down’ herbivory control. A question therefore arises as to how standing microbial biomass is regulated. Here, we present results from a survey of soil and rock microbial community metagenomes using the GeoChip microarray that demonstrate antibiotic resistance and phage infection are widespread. We interrogated a range of dry valley locations from maritime to extreme inland sites. Antibiotic resistance genes were identified in three categories: beta-lactamases, tetracycline and vanomycin plus a range of transporter genes. Frequency of recovery generally reflected microbial diversity, with greatest abundance among Halobacteria, Proteobacteria and the photosynthetic bacteria (Chlorobi, Chloroflexi and Cyanobacteria). However, no clear differences between locations and soil/rock communities were apparent. Phage signals were also recovered from all locations in soil and rock communities. The Leviviridae, Myoviridae, Podoviridae and Siphoviridae were ubiquitous . The Corticoviridae occurred only in moisturesufficient hyporheic soils, the Microviridae occurred only in maritime and hyporheic sites and an unidentified group within the order Caudovirales occurred only at dry inland sites. We postulate that widespread antibiotic resistance indicates potential inter-specific interaction and that phage signals indicate possible ‘bottom-up’ trophic regulation in the dry valleys.http://link.springer.com/journal/3002016-02-28hb201

Integrating the evidence for a terrestrial carbon sink caused by increasing atmospheric CO2

Atmospheric carbon dioxide concentration ([CO2]) is increasing, which increases leaf‐scale photosynthesis and intrinsic water‐use efficiency. These direct responses have the potential to increase plant growth, vegetation biomass, and soil organic matter; transferring carbon from the atmosphere into terrestrial ecosystems (a carbon sink). A substantial global terrestrial carbon sink would slow the rate of [CO2] increase and thus climate change. However, ecosystem CO2‐responses are complex or confounded by concurrent changes in multiple agents of global change and evidence for a [CO2]‐driven terrestrial carbon sink can appear contradictory. Here we synthesise theory and broad, multi‐disciplinary evidence for the effects of increasing [CO2] (iCO2) on the global terrestrial carbon sink. Evidence suggests a substantial increase in global photosynthesis since pre‐industry. Established theory, supported by experiments, indicates that iCO2 is likely responsible for about half of the increase. Global carbon budgeting, atmospheric data, and forest inventories indicate a historical carbon sink, and these apparent iCO2‐responses are high in comparison with experiments and theory. Plant mortality and soil carbon iCO2‐responses are highly uncertain. In conclusion, a range of evidence supports a positive terrestrial carbon sink in response to iCO2, albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change