Rhythmic interaction between Period1 mRNA and HnRNP Q leads to circadian time-dependent translation

The mouse PERIOD1 (mPER1) protein, along with other clock proteins, plays a crucial role in the maintenance of circadian rhythms. mPER1 also provides an important link between the circadian system and the cell cycle system. Here we show that the circadian expression of mPER1 is regulated by rhythmic translational control of mPer1 mRNA together with transcriptional modulation. This time-dependent translation was controlled by an internal ribosomal entry site (IRES) element in the 5' untranslated region (5'-UTR) of mPer1 mRNA along with the trans-acting factor mouse heterogeneous nuclear ribonucleoprotein Q (mhnRNP Q). Knockdown of mhnRNP Q caused a decrease in mPER1 levels and a slight delay in mPER1 expression without changing mRNA levels. The rate of IRES-mediated translation exhibits phase-dependent characteristics through rhythmic interactions between mPer1 mRNA and mhnRNP Q. Here, we demonstrate 5'-UTR-mediated rhythmic mPer1 translation and provide evidence for posttranscriptional regulation of the circadian rhythmicity of core clock genes.X112932sciescopu

Controlling Magnetic Anisotropy in a Zero-Dimensional S=1 Magnet Using Isotropic Cation Substitution

The [Zn_{1–x}_Ni-{x}(HF_{2})(pyz)_{2}]SbF_{6} (x = 0.2; pyz = pyrazine) solid solution exhibits a zero-field splitting (D) that is 22% larger [D = 16.2(2) K (11.3(2) cm^{–1})] than that observed in the x = 1 material [D = 13.3(1) K (9.2(1) cm^{–1)}]. The substantial change in D is accomplished by an anisotropic lattice expansion in the MN_{4} (M = Zn or Ni) plane, wherein the increased concentration of isotropic Zn(II) ions induces a nonlinear variation in M-F and M-N bond lengths. In this, we exploit the relative donor atom hardness, where M-F and M-N form strong ionic and weak coordinate covalent bonds, respectively, the latter being more sensitive to substitution of Ni by the slightly larger Zn(II) ion. In this way, we are able to tune the single-ion anisotropy of a magnetic lattice site by Zn-substitution on nearby sites. This effect has possible applications in the field of single-ion magnets and the design of other molecule-based magnetic systems

Remote Manipulation of Droplets on a Flexible Magnetically Responsive Film

The manipulation of droplets is used in a wide range of applications, from lab-on-a-chip devices to bioinspired functional surfaces. Although a variety of droplet manipulation techniques have been proposed, active, fast and reversible manipulation of pure discrete droplets remains elusive due to the technical limitations of previous techniques. Here, we describe a novel technique that enables active, fast, precise and reversible control over the position and motion of a pure discrete droplet with only a permanent magnet by utilizing a magnetically responsive flexible film possessing actuating hierarchical pillars on the surface. This magnetically responsive surface shows reliable actuating capabilities with immediate field responses and maximum tilting angles of ???90??. Furthermore, the magnetic responsive film exhibits superhydrophobicity regardless of tilting angles of the actuating pillars. Using this magnetically responsive film, we demonstrate active and reversible manipulation of droplets with a remote magnetic force.open0

Stage-Dependent Tolerance of the German Cockroach, Blattella germanica for Dichlorvos and Propoxur

Stage-dependent dichlorvos and propoxur tolerance in a field population of the German cockroach, Blattella germanica Linnaeus (Blatodea: Blattellidae), was investigated in the laboratory using a topical application bioassay. The results showed the 6 week-old nymphs were more tolerant to dichlorvos and propoxur than the other ages tested. LD50 values of dichlorvos and propoxur for the 6 week-old nymphs were 2.003 µµg per insect and 5.296 µµg per insect, respectively. Tolerance ratios of 18.55-fold and 4.98-fold for LD50 were obtained from 6-week-old nymphs compared to 4 week-old nymphs. The specific activity of acetylcholinesterase (AChE) from 1 week-old nymphs was the highest among all tested developmental stages of nymphs and adult males and females. The specific activity of AChE decreased significantly with increasing age. The sensitivity of AChE to dichlorvos was the highest with a ki value of 3.12××104 mol-1min-1 in the last nymphal stage of B. germanica (about 6 weeks-old). The AChE from 4 week-old nymphs was the most sensitive to propoxur, with the highest ki value being 2.63××105 mol-1min-1. These results indicated that the different developmental stages and sexes of B. germanica affected the inhibition of AChE by dichlorvos and propoxur

Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics.

Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives

Investigating the dynamics of surface-immobilized DNA nanomachines

Surface-immobilization of molecules can have a profound influence on their structure, function and dynamics. Toehold-mediated strand displacement is often used in solution to drive synthetic nanomachines made from DNA, but the effects of surface-immobilization on the mechanism and kinetics of this reaction have not yet been fully elucidated. Here we show that the kinetics of strand displacement in surface-immobilized nanomachines are significantly different to those of the solution phase reaction, and we attribute this to the effects of intermolecular interactions within the DNA layer. We demonstrate that the dynamics of strand displacement can be manipulated by changing strand length, concentration and G/C content. By inserting mismatched bases it is also possible to tune the rates of the constituent displacement processes (toehold-binding and branch migration) independently, and information can be encoded in the time-dependence of the overall reaction. Our findings will facilitate the rational design of surface-immobilized dynamic DNA nanomachines, including computing devices and track-based motors

The costs, resource use, and cost-effectiveness of Clinical Nurse Specialist (CNSs) led interventions for patients with palliative care needs: a systematic review of international evidence

Background: Patients with palliative care (PC) needs do not access specialist palliative care services according to their necessities. Clinical Nurse Specialists (CNS) working across a variety of fields are playing an increasingly important role in the care of such patients, but there is limited knowledge of the extent to which their interventions are cost-effective. Objectives: To present results from a systematic review of the international evidence on the costs, resource use and cost effectiveness of CNS led interventions for patients palliative care needs, defined as seriously ill patients and those with advanced disease or frailty who are unlikely to be cured, recover, or stabilize. Design: Systematic review following PRISMA methodology. Data sources: Medline, Embase, Cinahl and Cochrane library up to 2015. Studies focusing on the outcomes of CNS interventions for patients with PC needs, and including at least one economic outcome, were considered. The quality of studies was assessed using tools from the Joanna-Briggs-Institute. Results: A total of 79 papers were included: 37 RCTs, 22 quasi-experimental studies, 7 service evaluations and other studies, and 13 economic analyses. The studies included a wide variety of interventions including clinical, support and education, as well as care coordination activities. The quality of the studies varied greatly. Conclusions: CNSs interventions may be effective in reducing specific resource use such as hospitalizations /re-hospitalizations/admissions, length of stay, and health care costs. There is mixed evidence regarding their cost-effectiveness. Future studies should ensure that clinical nurse specialists’ roles and activities are clearly described and evaluated

Intrusion detection routers: Design, implementation and evaluation using an experimental testbed

In this paper, we present the design, the implementation details, and the evaluation results of an intrusion detection and defense system for distributed denial-of-service (DDoS) attack. The evaluation is conducted using an experimental testbed. The system, known as intrusion detection router (IDR), is deployed on network routers to perform online detection on any DDoS attack event, and then react with defense mechanisms to mitigate the attack. The testbed is built up by a cluster of sufficient number of Linux machines to mimic a portion of the Internet. Using the testbed, we conduct real experiments to evaluate the IDR system and demonstrate that IDR is effective in protecting the network from various DDoS attacks. © 2006 IEEE.published_or_final_versio