MicroRNAs (miRNAs) are small regulatory RNA molecules that inhibit the expression of specific target genes by binding to and cleaving their messenger RNAs or otherwise inhibiting their translation into proteins. miRNAs are transcribed as much larger primary transcripts (pri-miRNAs), the function of which is not fully understood. Here we show that plant pri-miRNAs contain short open reading frame sequences that encode regulatory peptides. The pri-miR171b of Medicago truncatula and the pri-miR165a of Arabidopsis thaliana produce peptides, which we term miPEP171b and miPEP165a, respectively, that enhance the accumulation of their corresponding mature miRNAs, resulting in downregulation of target genes involved in root development. The mechanism of miRNA-encoded peptide (miPEP) action involves increasing transcription of the pri-miRNA. Five other pri-miRNAs of A. thaliana and M. truncatula encode active miPEPs, suggesting that miPEPs are widespread throughout the plant kingdom. Synthetic miPEP171b and miPEP165a peptides applied to plants specifically trigger the accumulation of miR171b and miR165a, leading to reduction of lateral root development and stimulation of main root growth, respectively, suggesting that miPEPs might have agronomical applications.
Author Summary The ever growing amount of genomic data enables the assembly of large-scale network models that can provide important new insights into living systems. However, assembly and validation of such large-scale models can be challenging, since we often lack sufficient information to make accurate predictions. This work describes a new approach for constructing large-scale transcriptional regulatory networks of individual cells. We show that the reconstructed network captures a signif
Moderate consumption of wine seems to produce positive health effects derived from the occurrence of bioactive polyphenols. The gut microbiota is involved in the metabolism of phenolic compounds, and these compounds and/or their metabolites may modulate gut microbiota through the stimulation of the growth of beneficial bacteria and the inhibition of pathogenic bacteria. The characterization of bacterial metabolites derived from polyphenols is essential in order to understand their effects, inclu
щлThis is the first in a series of interviews highlighting the work of experts in the field of complex systems science. Dr. Ben Althouse, an Omidyar Fellow at the Santa Fe Institute, is a mathematical epidemiologist focusing on the dynamics of infectious disease transmission. Ben holds both an ScM in Biostatistics and a PhD in Epidemiology from the Johns Hopkins Bloomberg School of Public Health where he focused on understanding Dengue fever and other sylvatic mosquito-borne viruses (arboviruses) in Senegal using mechanistic modeling and the SIR model. Dr. Althouse also attended the Santa Fe Institute’s Complex Systems Summer School during his graduate studies.
Intestinal microbial communities have profound effects on host physiology. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined. Here we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Murine norovirus (MNV) infection of germ-free or antibiotic-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signalling. Consistent with this observation, the IFN-[agr] receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of treatment with antibiotics in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity, similarly to commensal bacteria.
Author Summary Though more than 20,000 binary protein-protein interactions have been published for a few well-studied bacterial species, the results rarely capture the full extent to which proteins take part in complexes. Here, we use experimentally-observed protein complexes from E . coli or Mycoplasma pneumoniae , as well as gene orthology, to predict protein complexes across many species of bacteria. Surprisingly, the majority of protein complexes is not conserved, demonstrating an une
Dmitry Alexeev's insight:
conservation of protein complex content is not constant in bacteria - is it because the places of some preitein in complexes were overtaken by other proteins?
how does it correspond to phylogeny and evolution?
Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of Information and Communication Technology (ICT): they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call “intelligence”. Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as “human” and “brain” out of the defining features of “intelligence”, all forms of life – from microbes to humans – exhibit some or all characteristics consistent with “intelligence”. We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo.
Dmitry Alexeev's insight:
Level of intelligence and computational mechanisms for intracellular calculations
The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.
Dmitry Alexeev's insight:
should we test the chemicals one by one - or finally have a preassumption of thier influence on gut?
The aquarium looks empty, but there is something in it. A pair of eyes stick out from the sandy floor, and their owner is easily scooped up into a glass bowl. At first, the creature looks like a hazelnut truffle — small, round and covered in tiny flecks. But with a gentle shake, the flecks of sand fall off to reveal a female Hawaiian bobtail squid (Euprymna scolopes), about the size of a thumb. As she jets furiously around the bowl, discs of pigment bloom and fade over her skin like a living pointillist painting.
There are no other animals in the bowl, but the squid is not alone. Its undersides contain a two-chambered light organ that is full of glowing bacteria called Vibrio fischeri. In the wild, their luminescence is thought to match the moonlight welling down from above and cancel out the squid's shadow, hiding the animal from predators. From below, the squid is invisible. From above, it is adorable. “They're just so beautiful,” says Margaret McFall-Ngai, a zoologist at the University of Wisconsin–Madison. “They're phenomenal lab animals.”
Few things excite McFall-Ngai more than the partnership between the bobtail squid and V. fischeri — and that is after studying it for more than 26 years. Over that time, she has shown that this symbiotic relationship is more intimate than anyone had imagined. She has found that the bacterium out-competes other microbes to establish an entirely faithful relationship with one host. It interacts with the squid's immune system, guides its body clock and shapes its early development by transforming its body.
eding/fasting cycle influence host metabolism and contribute to obesity and metabolic diseases. However, fundamental characteristics of this relationship between the feeding/fasting cycle and the gut microbiome are unknown. Our studies show that the gut microbiome is highly dynamic, exhibiting daily cyclical fluctuations in composition. Diet-induced obesity dampens the daily feeding/fasting rhythm and diminishes many of these cyclical fluctuations. Time-restricted feeding (TRF), in which feeding is consolidated to the nocturnal phase, partially restores these cyclical fluctuations. Furthermore, TRF, which protects against obesity and metabolic diseases, affects bacteria shown to influence host metabolism. Cyclical changes in the gut microbiome from feeding/fasting rhythms contribute to the diversity of gut microflora and likely represent a mechanism by which the gut microbiome affects host metabolism. Thus, feeding pattern and time of harvest, in addition to diet, are important parameters when assessing the microbiome’s contribution to host metabolism.
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