Oscillation patterns in negative feedback loops

Organisms are equipped with regulatory systems that display a variety of dynamical behaviours ranging from simple stable steady states, to switching and multistability, to oscillations. Earlier work has shown that oscillations in protein concentrations or gene expression levels are related to the presence of at least one negative feedback loop in the regulatory network. Here we study the dynamics of a very general class of negative feedback loops. Our main result is that in these systems the sequence of maxima and minima of the concentrations is uniquely determined by the topology of the loop and the activating/repressing nature of the interaction between pairs of variables. This allows us to devise an algorithm to reconstruct the topology of oscillating negative feedback loops from their time series; this method applies even when some variables are missing from the data set, or if the time series shows transients, like damped oscillations. We illustrate the relevance and the limits of validity of our method with three examples: p53-Mdm2 oscillations, circadian gene expression in cyanobacteria, and cyclic binding of cofactors at the estrogen-sensitive pS2 promoter.Comment: 10 pages, 8 figure

Analysis of Arm Movement Strategy in Virtual Catching Task

In this paper, we explored how the arm movement pattern as well as the related strategy of the children with Cerebral Palsy (CP) and the healthy children can be changed in the virtual catching task on a previously proposed rehabilitation system. We recruited 50 healthy children from elementary school, and 3 children with CP as subjects to classify their arm movement pattern/strategy. As a result of the classification, we identified three arm movement stages : Initial position, Reaching path, and Waving form, as well as movement pattern strategy under each movement stage. Based on the classified pattern, we compared the differences in the time series changes of movement strategy between healthy children and the children with CP. The results show there is a significant difference in the strategy of arm movements in the Initial position between healthy and CP children

Prototype Analog Front-end for Negative-ion Gas and Dual-phase Liquid-Ar TPCs

We report on the recent development of a versatile analog front-end compatible with a negative-ion $\mu$-TPC for a directional dark matter search as well as a dual-phase, next-generation $\mathcal{O}$(10~kt) liquid argon TPC to study neutrino oscillations, nucleon decay, and astrophysical neutrinos. Although the operating conditions for negative-ion and liquid argon TPCs are quite different (room temperature \textit{vs.} $\sim$88~K operation, respectively), the readout electronics requirements are similar. Both require a wide-dynamic range up to 1600 fC, and less than 2000--5000 e$^-$ noise for a typical signal of 80 fC with a detector capacitance of $C_{\rm det} \approx 300$~pF. In order to fulfill such challenging requirements, a prototype ASIC was newly designed using 180-nm CMOS technology. Here, we report on the performance of this ASIC, including measurements of shaping time, dynamic range, and equivalent noise charge (ENC). We also demonstrate the first operation of this ASIC on a low-pressure negative-ion $\mu$-TPC.Comment: accepted by JINS

Circadian rhythms in prokaryotes: luciferase as a reporter of circadian gene expression in cyanobacteria.

We have used a luciferase reporter gene and continuous automated monitoring of bioluminescence to demonstrate unequivocally that cyanobacteria exhibit circadian behaviors that are fundamentally the same as circadian rhythms of eukaryotes. We also show that these rhythms can be studied by molecular methods in Synechococcus sp. PCC7942, a strain for which genetic transformation is well established. A promoterless segment of the Vibrio harveyi luciferase structural genes (luxAB) was introduced downstream of the promoter for the Synechococcus psbAI gene, which encodes a photosystem II protein. This reporter construction was recombined into the Synechococcus chromosome, and bioluminescence was monitored under conditions of constant illumination following entrainment to light and dark cycles. The reporter strain, AMC149, expressed a rhythm of bioluminescence which satisfies the criteria of circadian rhythms: persistence in constant conditions, phase resetting by light/dark signals, and temperature compensation of the period. Rhythmic changes in levels of the native psbAI message following light/dark entrainment supported the reporter data. The behavior of this prokaryote disproves the dogma that circadian mechanisms must be based on eukaryotic cellular organization. Moreover, the cyanobacterial strain described here provides an efficient experimental system for molecular analysis of the circadian clock

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Development of highly radiopure NaI(Tl) scintillator for PICOLON dark matter search project

Highly radiopure NaI(Tl) was developed to search for particle candidates of dark matter. Optimized methods were combined to reduce various radioactive impurities. 40K was effectively reduced by the recrystallization method. The progenies of the decay chains of uranium and thorium were reduced by appropriate resins. The concentration of natural potassium in NaI(Tl) crystal was reduced to 20 ppb. Concentrations of alpha-ray emitters were successfully reduced by appropriate resin selection. The present concentrations of the thorium series and 226Ra were 1.2±1.4μBq/kg and 13±4μBq/kg, respectively. No significant excess in the concentration of 210Pb was obtained, and the upper limit was 5.7 μBq/kg at 90% CL. The achieved level of radiopurity of NaI(Tl) crystals makes the construction of a dark matter detector possible

PICOLON dark matter search project

PICOLON (Pure Inorganic Crystal Observatory for LOw-energy Neutr(al)ino) aims to search for cosmic dark matter by high purity NaI(Tl) scintillator. We developed extremely pure NaI(Tl) crystal by hybrid purification method. The recent result of 210Pb in our NaI(Tl) is less than 5.7 μBq/kg. We will report the test experiment in the low-background measurement at Kamioka Underground Laboratory. The sensitivity for annual modulating signals and finding dark matter particles will be discussed

The 5′ Flanking Region and Intron1 of the Bovine Prion Protein Gene (PRNP) Are Responsible for Negative Feedback Regulation of the Prion Protein

Transcription factors regulate gene expression by controlling the transcription rate. Some genes can repress their own expression to prevent over production of the corresponding protein, although the mechanism and significance of this negative feedback regulation remains unclear. In the present study, we describe negative feedback regulation of the bovine prion protein (PrP) gene PRNP in Japanese Black cattle. The PrP-expressing plasmid pEF-boPrP and luciferase-expressing plasmids containing the partial promoter fragment of PRNP incorporating naturally occurring single-nucleotide or insertion/deletion polymorphisms were transfected into N2a cells. Transfection of pEF-boPrP induced PrP overexpression and decreased the promoter activity of PRNP in the wild-type haplotype (23-bp Del, 12-bp Del, and −47C). Reporter gene assays further demonstrated that the 12- and 23-bp Ins/Del polymorphisms, which are thought to be associated with Sp1 (Specific protein 1) and RP58 (Repressor Protein with a predicted molecular mass of 58 kDa), in intron1 and the upstream region, respectively, and an additional polymorphism (−47C→A) in the Sp1-binding site responded differently to PrP overexpression. With the −47C SNP, the presence of the Del in either the 23-bp Ins/Del or the 12-bp Ins/Del allele was essential for the negative feedback caused by PrP overexpression. Furthermore, deletion mutants derived from the wild-type haplotype showed that nucleotides −315 to +2526, which include the 5′-flanking region and exon1, were essential for the response. These results indicate that certain negative feedback response elements are located in these sequences, suggesting that regulation by transcription factors such as Sp1 and RP58 may contribute to the negative feedback mechanism of PRNP