The Roles of Post-translational Modifications on α-Synuclein in the Pathogenesis of Parkinson’s Diseases

Parkinson’s disease is the second most common neurodegenerative disorder. Although the pathogenesis of Parkinson’s disease is not entirely clear, the aberrant aggregation of α-synuclein has long been considered as an important risk factor. Elucidating the mechanisms that influence the aggregation of α-synuclein is essential for developing an effective diagnostic, preventative and therapeutic strategy to treat this devastating disease. The aggregation of α-synuclein is influenced by several post-translational modifications. Here, we summarized the major post-translational modifications (phosphorylation, ubiquitination, truncation, nitration, O-GlcNAcylation) of α-synuclein and the effect of these modifications on α-synuclein aggregation, which may provide potential targets for future therapeutics

A γ\gamma-ray Quasi-Periodic modulation in the Blazar PKS 0301−-243?

We report a nominally high-confidence $\gamma$-ray quasi-periodic modulation in the blazar PKS 0301$-$243. For this target, we analyze its \emph{Fermi}-LAT Pass 8 data covering from 2008 August to 2017 May. Two techniques, i.e., the maximum likelihood optimization and the exposure-weighted aperture photometry, are used to build the $\gamma$-ray light curves. Then both the Lomb-Scargle Periodogram and the Weighted Wavelet Z-transform are applied to the light curves to search for period signals. A quasi-periodicity with a period of $2.1\pm0.3$ yr appears at the significance level of $\sim5\sigma$, although it should be noted that this putative quasi-period variability is seen in a data set barely four times longer. We speculate that this $\gamma$-ray quasi-periodic modulation might be evidence of a binary supermassive black hole.Comment: 9 pages, 8 figures; Accepted for publication in Ap

EFFECTS OF SEAT POSITION ON THE JOINT MOMENTS OF THE LOWER EXTREMITIES DURING CYCLING IN THE ELDERLY

The purpose of this study was to quantify the joint moments of the lower extremities with different seat positions during cycling in elderly. Fifteen older adults performed cycling on a self-developed bicycle ergometer at three horizontal and three vertical seat positions. The pedals were instrumented with six-component load cells to measure pedal reaction forces; and a motion capture system was used to measure body segment kinematic data. Both data sets were used to calculate joint moments during a crank cycle. The results showed that seat positions affected joint moments significantly, especially the horizontal positions. A more posterior seat position led to a more balanced loading at the hip and knee, with less peak muscle loadings. The results will be helpful for cycle design and fitting for the elderly

IMAGE-BASED MEASUREMENT AND BIOMECHANICAL ANALYSIS OF THE KNEE JOINT DURING FUNCTIONAL ACTIVITIES

A new approach based on the integration of medical image-based measurement techniques, infrared stereophotogrammetry and finite element modelling (FEM) was developed for comprehensive subject-specific biomechanical analyses of the knee joint during weight-bearing functional activities including cycling. The medical image-based methods include digitally reconstructed radiograph (DRR) based 3D fluoroscopy methods, and a new slice-to-volume registration method using FLASH MRI for the real-time measurement of the 3D kinematics of the knee in vivo. With the new approach, the soft tissue artefacts associated with skin marker-based stereophotogrammetry and their effects on the calculated biomechanical variables were also investigated

EFFECTS OF SEAT POSITION ON JOINT LOADS OF THE UPPER EXTREMITIES DURING HANDCYCLING IN WHEELCHAIR-DEPENDENT INDIVIDUALS

The current study aimed to quantify the joint moments of the upper extremities with different seat positions during handcycling in wheelchair-dependent individuals. Sixteen subjects performed handcycling while the handgrip reaction forces were measured by a handgrip instrumented with a six-component load cell and body segment kinematic data by a motion capture system. Both data sets were used to calculate joint moments of the upper limbs during a crank cycle. The loads at the shoulder were affected mostly by the vertical seat positions. The higher the seat, the greater loads transmitted by the muscles with relatively greater strength. The current data will be helpful for future handcycle design and fitting for wheelchair-dependent individuals

Prokineticin 2 Is a Target Gene of Proneural Basic Helix-Loop-Helix Factors for Olfactory Bulb Neurogenesis

Prokineticin 2, a cysteine-rich secreted protein, regulates diverse biological functions including the neurogenesis of olfactory bulb. Here we show that the PK2 gene is a functional target gene of proneural basic helix-loop-helix (bHLH) factors. Neurogenin 1 and MASH1 activate PK2 transcription by binding to E-box motifs on the PK2 promoter with the same set of E-boxes critical for another pair of bHLH factors, CLOCK and BMAL1, in the regulation of circadian clock. Our results establish PK2 as a common functional target gene for different bHLH transcriptional factors in mediating their respective functions