We live in a macroscopic three-dimensional world, but our best description of the structure of matter is at the atomic and molecular scale. Understanding the relationship between the two scales requires that we bridge from the molecular world to the macroscopic world. Connecting these two domains with atomic precision is a central goal of the natural sciences, but it requires high spatial control of the 3D structure of matter.1 The simplest practical route to producing precisely designed 3D macroscopic objects is to form a crystalline arrangement by self-assembly, because such a periodic array has only conceptually simple requirements: [1] A motif whose 3D structure is robust, [2] dominant affinity interactions between parts of the motif when it self-associates, and [3] a predictable structures for these affinity interactions. Fulfilling all these criteria to produce a 3D periodic system is not easy, but it should readily be achieved by well-structured branched DNA motifs tailed by sticky ends.2 Complementary sticky ends associate with each other preferentially and assume the well-known B-DNA structure when they do so;3 the helically repeating nature of DNA facilitates the construction of a periodic array. It is key that the directions of propagation associated with the sticky ends not share the same plane, but extend to form a 3D arrangement of matter. Here, we report the crystal structure at 4 Å resolution of a designed, self-assembled, 3D crystal based on the DNA tensegrity triangle.4 The data demonstrate clearly that it is possible to design and self-assemble a well-ordered macromolecular 3D crystalline lattice with precise control.
Spore killers in fungi are selfish genetic elements that distort Mendelian segregation in their favor. It remains unclear how many species harbor them and how diverse their mechanisms are. Here, we discover two spore killers from a natural isolate of the fission yeast Schizosaccharomyces pombe. Both killers belong to the previously uncharacterized wtf gene family with 25 members in the reference genome. These two killers act in strain-background-independent and genome-location-independent manners to perturb the maturation of spores not inheriting them. Spores carrying one killer are protected from its killing effect but not that of the other killer. The killing and protecting activities can be uncoupled by mutation. The numbers and sequences of wtf genes vary considerably between S. pombe isolates, indicating rapid divergence. We propose that wtf genes contribute to the extensive intraspecific reproductive isolation in S. pombe, and represent ideal models for understanding how segregation-distorting elements act and evolve.DOI: http://dx.doi.org/10.7554/eLife.26057.001
BackgroundMicroglial activation plays an important role in neurodegenerative diseases through production of nitric oxide (NO) and several pro-inflammatory cytokines. Lipoxins (LXs) and aspirin-triggered LXs (ATLs) are considered to act as 'braking signals' in inflammation. In the present study, we investigated the effect of aspirin-triggered LXA4 (ATL) on infiammatory responses induced by lipopolysaccharide (LPS) in murine microglial BV-2 cells.MethodsBV-2 cells were treated with ATL prior to LPS exposure, and the effects of such treatment production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were analysed by Griess reaction, ELISA, western blotting and quantitative RT-PCR. Moreover, we investigated the effects of ATL on LPS-induced nuclear factor-κB (NF-κB) activation, phosphorylation of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) activation.ResultsATL inhibited LPS-induced production of NO, IL-1β and TNF-α in a concentration-dependent manner. mRNA expressions for iNOS, IL-1β and TNF-α in response to LPS were also decreased by ATL. These effects were inhibited by Boc-2 (a LXA4 receptor antagonist). ATL significantly reduced nuclear translocation of NF-κB p65, degradation of the inhibitor IκB-α, and phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK in BV-2 cells activated with LPS. Furthermore, the DNA binding activity of NF-κB and AP-1 was blocked by ATL.ConclusionsThis study indicates that ATL inhibits NO and pro-inflammatory cytokine production at least in part via NF-κB, ERK, p38 MAPK and AP-1 signaling pathways in LPS-activated microglia. Therefore, ATL may have therapeutic potential for various neurodegenerative diseases.
Mikania micrantha is one of the top 100 worst invasive species that can cause serious damage to natural ecosystems and substantial economic losses. Here, we present its 1.79 Gb chromosome-scale reference genome. Half of the genome is composed of long terminal repeat retrotransposons, 80% of which have been derived from a significant expansion in the past one million years. We identify a whole genome duplication event and recent segmental duplications, which may be responsible for its rapid environmental adaptation. Additionally, we show that M. micrantha achieves higher photosynthetic capacity by CO 2 absorption at night to supplement the carbon fixation during the day, as well as enhanced stem photosynthesis efficiency. Furthermore, the metabolites of M. micrantha can increase the availability of nitrogen by enriching the microbes that participate in nitrogen cycling pathways. These findings collectively provide insights into the rapid growth and invasive adaptation.
We describe the self-assembly of a DNA crystal that contains two tensegrity triangle molecules per asymmetric unit. We have used X-ray crystallography to determine its crystal structure. In addition, we have demonstrated control over the colors of the crystals by attaching either Cy3 dye (pink) or Cy5 dye (blue-green) to the components of the crystal, yielding crystals of corresponding colors. Attaching the pair of dyes to the pair of molecules yields a purple crystal.
Bacterial infections in wounds often delay the healing process, and may seriously threaten human life. It is urgent to develop wound dressings to effectively detect and treat bacterial infections. Nanoparticles have been extensively used in wound dressings because of their specific properties. This review highlights the recent progress on nanoparticle-based wound dressings for bacterial detection and therapy. Specifically, nanoparticles have been applied as intrinsic antibacterial agents or drug delivery vehicles to treat bacteria in wounds. Moreover, nanoparticles with photothermal or photodynamic property have also been explored to endow wound dressings with significant optical properties to further enhance their bactericidal effect. More interestingly, nanoparticle-based smart dressings have been recently explored for bacteria detection and treatment, which enables an accurate assessment of bacterial infection and a more precise control of on-demand therapy.
Double cohesion has proved to be a useful tool to assemble robust 2D arrays of large tiles. Here we present a variety of examples showing the utility of this approach. We apply this principle to the 3 types of 2D lattice sections of arrays whose individual tiles are inherently 3 dimensional, because they contain three vectors that span 3-space. This application includes motifs which are based on the tensegrity triangle, the six-helix bundle motif and on three skewed triple crossover molecules. All of these designs have the potential to form 3 dimensional structures if all three directions of propagation are allowed. If one direction is blunted, 2D arrays form, and all 3 combinations are presented here. In addition, a large parallelogram array that was not attainable previously using single duplex cohesion was also constructed using double cohesion. For comparison, arrays which use another type of double cohesion, double paranemic (PX) cohesion are also presented. Double cohesion of sticky ends proved to be the more effective tool to assemble large motifs into arrays.
Mutations in the presenilin (PSEN1 and PSEN2) genes are linked to familial Alzheimer's disease (AD) and cause loss of its essential function. Complete inactivation of presenilins in excitatory neurons of the adult mouse cerebral cortex results in progressive memory impairment and age-dependent neurodegeneration, recapitulating key features of AD. In this study, we examine the effects of varying presenilin dosage on cortical neuron survival by generating presenilin-1 conditional knock-out (PS1 cKO) mice carrying two, one, or zero copies of the PS2 gene. We found that PS1 cKO;PS2 ϩ/Ϫ mice at 16 months exhibit marked neurodegeneration in the cerebral cortex with ϳ17% reduction of cortical volume and neuron number, as well as astrogliosis and microgliosis compared with ϳ50% reduction of cortical volume and neuron number in PS1 cKO;PS2 Ϫ/Ϫ mice. Moreover, there are more apoptotic neurons labeled by activated caspase-3 immunoreactivity and TUNEL assay in PS1 cKO;PS2 ϩ/Ϫ mice at 16 months, whereas apoptotic neurons are increased in the PS1 cKO; PS2 Ϫ / Ϫ cerebral cortex at 4 months. The accumulation of the C-terminal fragments of the amyloid precursor protein is inversely correlated with PS dosage. Interestingly, levels of PS2 are higher in the cerebral cortex of PS1 cKO mice, suggesting a compensatory upregulation that may provide protection against neurodegeneration in these mice. Together, our findings show that partial to complete loss of presenilin activity causes progressively more severe neurodegeneration in the mouse cerebral cortex during aging, suggesting that impaired presenilin function by PSEN mutations may lead to neurodegeneration and dementia in AD.
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