Circadian clocks optimally adapt to sunlight for reliable synchronization

Circadian oscillation provides selection advantages through synchronization to the daylight cycle. However, a reliable clock must be designed through two conflicting properties: entrainability to synchronize internal time with periodic stimuli such as sunlight, and regularity to oscillate with a precise period. These two aspects do not easily coexist because better entrainability favors higher sensitivity, which may sacrifice the regularity. To investigate conditions for satisfying the two properties, we analytically calculated the optimal phase-response curve with a variational method. Our result indicates an existence of a dead zone, i.e., a time period during which input stimuli neither advance nor delay the clock. A dead zone appears only when input stimuli obey the time course of actual solar radiation but a simple sine curve cannot yield a dead zone. Our calculation demonstrates that every circadian clock with a dead zone is optimally adapted to the daylight cycle.Comment: 24 pages, 7 figure

Fluctuating noise drives Brownian transport

The transport properties of Brownian ratchet was studied in the presence of stochastic intensity noise (SIN) in both overdamped and underdamped regimes. In the overdamped case, analytical solution using the matrix continued fraction method revealed the existence of a maximum current when the noise intensity fluctuates on intermediate time scale regions. Similar effects were observed for the underdamped case by Monte Carlo simulations. The optimal time-correlation for the Brownian transport coincided with the experimentally observed time-correlation of the extrinsic noise in Esherichia coli gene expression and implied the importance of environmental noise for molecular mechanisms.Comment: 22 pages, 8 figure

Enhanced entrainability of genetic oscillators by period mismatch

Biological oscillators coordinate individual cellular components so that they function coherently and collectively. They are typically composed of multiple feedback loops, and period mismatch is unavoidable in biological implementations. We investigated the advantageous effect of this period mismatch in terms of a synchronization response to external stimuli. Specifically, we considered two fundamental models of genetic circuits: smooth- and relaxation oscillators. Using phase reduction and Floquet multipliers, we numerically analyzed their entrainability under different coupling strengths and period ratios. We found that a period mismatch induces better entrainment in both types of oscillator; the enhancement occurs in the vicinity of the bifurcation on their limit cycles. In the smooth oscillator, the optimal period ratio for the enhancement coincides with the experimentally observed ratio, which suggests biological exploitation of the period mismatch. Although the origin of multiple feedback loops is often explained as a passive mechanism to ensure robustness against perturbation, we study the active benefits of the period mismatch, which include increasing the efficiency of the genetic oscillators. Our findings show a qualitatively different perspective for both the inherent advantages of multiple loops and their essentiality.Comment: 28 pages, 13 figure

NADase as a target molecule of in vivo suppression of the toxicity in the invasive M-1 group A Streptococcal isolates

<p>Abstract</p> <p>Background</p> <p>NAD-glycohydrolase (NADase) secreted by M-1 group A streptococcal (GAS) isolates are suspected as one of the virulence factors to cause severe invasive disease including streptococcal toxic shock-like syndrome (STSS). M-1 GAS strains were divided into three groups based on NADase activity: high activity, low activity and no activity in our previous report.</p> <p>Results</p> <p>The representative high activity isolates taken from STSS patients showed higher virulence compared with isolates from the low activity group, when used to infect mice. The knockout mutant of the <it>nga </it>gene, which encodes NADase also showed reduced virulence in a mouse infection study. The cloned <it>nga </it>gene was able to significantly complement the lost virulence. In addition, the solution containing purified recombinant IFS, which is an inhibitor of NADase, partially rescued mice infected with <it>S. pyogenes</it>.</p> <p>Conclusions</p> <p>These results indicate that NADase is important for the virulence of <it>S. pyogenes </it>in vivo and is the potential target to suppress the virulence.</p

Myelopathy Caused by Chronic Epidural Hematoma Associated with L1 Osteoporotic Vertebral Collapse: A Case Report and Review of the Literature

Epidural hematoma associated with osteoporotic vertebral collapse has not been reported yet in the literature. We report a case of myelopathy caused by chronic epidural hematoma associated with L1 osteoporotic vertebral collapse and review the relevant literature

Ectopic Calcification as Discernible Manifestation in Neonates with Pseudohypoparathyroidism Type 1a

The diagnosis of pseudohypoparathyroidism type 1a (PHP1a) is challenging, because both the osteodystrophy, such as brachydactyly and round face, and the symptomatic hypocalcemia usually develop beyond infancy. Although ectopic calcification may be an early sign of PHP1a, there are no systematic reviews regarding the time of its appearance. We here report on two PHP1a patients who presented with subcutaneous calcification in neonatal period