Dysfunction of postural adjustments associated with voluntary movements in a mouse model of spinocerebellar ataxia type 3

Abstract-We investigated kinematics of the hindlimb and electromyographic activities of the hindlimb muscles in the mouth reaching task needing postural adjustments in a mouse model of spinocerebellar ataxia type 3 (SCA3). The mouse model of SCA3 showed the dysfunction of the postural adjustments. The results indicate that the cerebellum play an important role in the postural adjustments associated with the intended movements

Contributions of phase resetting and interlimb coordination to the adaptive control of hindlimb obstacle avoidance during locomotion in rats: a simulation study.

Obstacle avoidance during locomotion is essential for safe, smooth locomotion. Physiological studies regarding muscle synergy have shown that the combination of a small number of basic patterns produces the large part of muscle activities during locomotion and the addition of another pattern explains muscle activities for obstacle avoidance. Furthermore, central pattern generators in the spinal cord are thought to manage the timing to produce such basic patterns. In the present study, we investigated sensory-motor coordination for obstacle avoidance by the hindlimbs of the rat using a neuromusculoskeletal model. We constructed the musculoskeletal part of the model based on empirical anatomical data of the rat and the nervous system model based on the aforementioned physiological findings of central pattern generators and muscle synergy. To verify the dynamic simulation by the constructed model, we compared the simulation results with kinematic and electromyographic data measured during actual locomotion in rats. In addition, we incorporated sensory regulation models based on physiological evidence of phase resetting and interlimb coordination and examined their functional roles in stepping over an obstacle during locomotion. Our results show that the phase regulation based on interlimb coordination contributes to stepping over a higher obstacle and that based on phase resetting contributes to quick recovery after stepping over the obstacle. These results suggest the importance of sensory regulation in generating successful obstacle avoidance during locomotion

Phytoestrogens

Collectively, plants contain several different families of natural products among which are compounds with weak estrogenic or antiestrogenic activity toward mammals. These compounds, termed phytoestrogens, include certain isoflavonoids, flavonoids, stilbenes, and lignans. The best-studied dietary phytoestrogens are the soy isoflavones and the flaxseed lignans. Their perceived health beneficial properties extend beyond hormone-dependent breast and prostate cancers and osteoporosis to include cognitive function, cardiovascular disease, immunity and inflammation, and reproduction and fertility. In the future, metabolic engineering of plants could generate novel and exquisitely controlled dietary sources with which to better assess the potential health beneficial effects of phytoestrogens

Missense allele of a single nucleotide polymorphism rs2294008 attenuated antitumor effects of prostate stem cell antigen in gallbladder cancer cells

Background: Prostate stem cell antigen (PSCA), an organ-dependent tumor suppressor, is down regulated in gallbladder cancer (GBC). It is anticipated that the missense allele C of the single nucleotide polymorphism (SNP) rs2294008 (T/C) in the translation initiation codon of the gene affects the gene′s biological function and has some influence on GBC susceptibility. We examined the biological effect of the C allele on the function of the gene and the relation between the C allele and GBC susceptibility. Materials and Methods: Functional analysis of the SNP was conducted by introducing PSCA cDNA harboring the allele to a GBC cell line TGBC- 1TKB and performing colony formation assays in vitro and tumor formation assays in mice. The effect on transcriptional regulation was assessed by reporter assays. The association study was conducted on 44 Japanese GBC cases and 173 controls. Results: The PSCA cDNA harboring the C allele showed lower cell growth inhibition activity (20% reduction) than that with the T allele. Concordantly, when injected into subcutaneous tissues of mice, the GBC cell line stably expressing the cDNA with the C allele formed tumors of almost the same size as that of the control cells, but the cell line expressing the cDNA with the T allele showed slower growth. The upstream DNA fragment harboring the C allele had more transcriptional activity than that with the T allele. The C allele showed positive correlation to GBC but no statistical significant odds ratio (OR = 1.77, 95% confidence interval 0.85-3.70, P value = 0.127 in dominant model). Conclusions: The missense allele was shown to have a biological effect, attenuating antitumor activities of PSCA, and consequently it may be a potential risk for GBC development. An association study in a larger sample size may reveal a significant association between the allele and GBC

Natural isoflavones regulate the quadruplex–duplex competition in human telomeric DNA

Effects of natural isoflavones on the structural competition of human telomeric G-quadruplex d[AG3(T2AG3)3] and its related Watson–Crick duplex d[AG3(T2AG3)3-(C3TA2)3C3T] are investigated by using circular dichroism (CD), ESI-MS, fluorescence quenching measurement, CD stopped-flow kinetic experiment, UV spectroscopy and molecular modeling methods. It is intriguing to find out that isoflavones can stabilize the G-quadruplex structure but destabilize its corresponding Watson–Crick duplex and this discriminated interaction is intensified by molecular crowding environments. Kinetic experiments indicate that the dissociation rate of quadruplex (kobs290 nm) is decreased by 40.3% at the daidzin/DNA molar ratio of 1.0 in K+, whereas in Na+ the observed rate constant is reduced by about 12.0%. Furthermore, glycosidic daidzin significantly induces a structural transition of the polymorphic G-quadruplex into the antiparallel conformation in K+. This is the first report on the recognition of isoflavones with conformational polymorphism of G-quadruplex, which suggests that natural isoflavone constituents potentially exhibit distinct regulation on the structural competition of quadruplex versus duplex in human telomeric DNA

Simpira v2: A Family of Efficient Permutations Using the AES Round Function

International audienceThis paper introduces Simpira, a family of cryptographic permutations that supports inputs of 128*b bits, where b is a positive integer. Its design goal is to achieve high throughput on virtually all modern 64-bit processors, that nowadays already have native instructions for AES. To achieve this goal, Simpira uses only one building block: the AES round function. For b=1, Simpira corresponds to 12-round AES with fixed round keys, whereas for b>=2, Simpira is a Generalized Feistel Structure (GFS) with an F-function that consists of two rounds of AES. We claim that there are no structural distinguishers for Simpira with a complexity below 2^128, and analyze its security against a variety of attacks in this setting. The throughput of Simpira is close to the theoretical optimum, namely, the number of AES rounds in the construction. For example, on the Intel Skylake processor, Simpira has throughput below 1 cycle per byte for b≤4 and b=6. For larger permutations, where moving data in memory has a more pronounced effect, Simpira with b=32 (512 byte inputs) evaluates 732 AES rounds, and performs at 824 cycles (1.61 cycles per byte), which is less than 13% off the theoretical optimum. If the data is stored in interleaved buffers, this overhead is reduced to less than 1%. The Simpira family offers an efficient solution when processing wide blocks, larger than 128 bits, is desired

Phase-dependent response to afferent stimulation during fictive locomotion: a computational modeling study

Central pattern generators (CPGs) in the spinal cord generate rhythmic neural activity and control locomotion in vertebrates. These CPGs operate under the control of sensory feedback that affects the generated locomotor pattern and adapt it to the animal's biomechanics and environment. Studies of the effects of afferent stimulation on fictive locomotion in immobilized cats have shown that brief stimulation of peripheral nerves can reset the ongoing locomotor rhythm. Depending on the phase of stimulation and the stimulated nerve, the applied stimulation can either shorten or prolong the current locomotor phase and the locomotor cycle. Here, we used a mathematical model of a half-center CPG to investigate the phase-dependent effects of brief stimulation applied to CPG on the CPG-generated locomotor oscillations. The CPG in the model consisted of two half-centers mutually inhibiting each other. The rhythmic activity in each half-center was based on a slowly inactivating, persistent sodium current. Brief stimulation was applied to CPG half-centers in different phases of the locomotor cycle to produce phase-dependent changes in CPG activity. The model reproduced several results from experiments on the effect of afferent stimulation of fictive locomotion in cats. The mechanisms of locomotor rhythm resetting under different conditions were analyzed using dynamic systems theory methods