Association of specific biotypes in patients with Parkinson disease and disease progression

Objective: To identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression. Methods: In this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314, age 61.0 ± 9.5, years 34.1% female, 5 years of follow-up). Voxel-level neuroanatomic features were estimated with deformation-based morphometry (DBM) of T1-weighted MRI. Voxels with deformation values that were significantly correlated (p < 0.01) with clinical scores (Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale Parts I–III and total score, tremor score, and postural instability and gait difficulty score) at baseline were selected. Then, these neuroanatomic features were subjected to hierarchical cluster analysis. Changes in the longitudinal progression and neuroanatomic pattern were compared between different biotypes. Results: Two neuroanatomic biotypes were identified: biotype 1 (n = 114) with subcortical brain volumes smaller than heathy controls and biotype 2 (n = 200) with subcortical brain volumes larger than heathy controls. Biotype 1 had more severe motor impairment, autonomic dysfunction, and much worse REM sleep behavior disorder than biotype 2 at baseline. Although disease durations at the initial visit and follow-up were similar between biotypes, patients with PD with smaller subcortical brain volume had poorer prognosis, with more rapid decline in several clinical domains and in dopamine functional neuroimaging over an average of 5 years. Conclusion: Robust neuroanatomic biotypes exist in PD with distinct clinical and neuroanatomic patterns. These biotypes can be detected at diagnosis and predict the course of longitudinal progression, which should benefit trial design and evaluation

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Blind Spots Analysis of Magnetic Tensor Localization Method

In order to compare and analyze the positioning efficiency of the magnetic tensor location method, this paper studies the blind spots of the magnetic tensor location method. By constructing two magnetic tensor localization models, the localization principles of the single-point magnetic tensor localization method (STLM) and the two-point magnetic tensor linear localization method (TTLM) are analyzed. Furthermore, the eigenvalue analysis method is studied to analyze the blind spots of STLM, and the spherical analysis method is proposed to analyze the blind spots of TTLM. The results show that when the direction of any measuring point is perpendicular to the direction of the target magnetic moment, blind spots of STLM appear. However, TTLM still has good positioning performance in the blind spot

The Morphological Structure, Physiological and Biochemical Changes During Sorus Development of Saccharina japonica

The reproductive characteristics of some hybrids from crosses of cultivated strains with wild populations are more similar to their wild parents. These hybrids form sorus twice a year in spring and autumn, unlike the conventional cultivars, which formed sorus once a year in summer. The S. japonica seedling industry begins in August in the north of China. However, hybrids form sorus in September or later. Therefore, these hybrids cannot be used as parental stock in the cultivation of summer seedlings in the north of China, hindering the promotion and application of these hybrids with excellent traits. Unfortunately, very few studies have focused on the induction and mechanism of sorus formation in kelp. It was of great significance to explore artificial induction technology for sorus formation of kelp hybrids and ensure the timely formation of sorus when the summer seedling cultivation based on an understanding of the biological process of sorus development. At present, research on the biological processes and characteristics of hybrid kelp sorus were limited. This study investigated the hybrid variety "Yudai No. 1". Discs from the kelp sporophytes were cultured in inflatable bottles. The sorus development process was divided into five stages (SA~SE) based on the appearance and morphological changes of the sorus. Samples for each stage were collected separately. The appearance, morphology, and tissue structure changes during the formation and development of sorus were systematically observed. Changes in the physiological and biochemical characteristics at different stages were also quantitatively studied. During sorus development, the surface of the sporophyte was smooth at stage SA, frosted in stage SB, noticeably protruded at stage SC, the cuticle at the apex of the paraphysis cells broken at stage SD, and the cuticle was smooth again in stage SE. The process was accompanied by the protrusion of epidermal cells (SB), the elongation of paraphysis cell (SC), the differentiation and development of sporoblast (SC, SD), and the formation and release of zoospores (SE). The cells (paraphysis cell and sporoblast) varied significantly and were constantly elongating at all stages (P < 0.05). The cells were especially elongated during the stage of zoospore formation and release (SE), zoospore cells were nearly 1-fold longer than the zoospores that were not released at stage SD. During the development of S. japonica sorus, the accumulation of nitrogen by sorus continued to increase, and there was little change after reaching the maximum level at stage SD. The formation of sorus was accompanied by the accumulation of nutrients. The protein content increased significantly in the early stages of sorus development and decreased at the stage of zoospore release. The protein content was significantly higher in the SC stage than that at stage SA (P < 0.05). Subsequently, the decline began after the SC stage, indicating the development of the sorus was the main biological activity, and the metabolic level was gradually reduced. Unlike that in previous studies, we identified a significant increase in the chlorophyll content during sorus development, which probably ensured all zoospores include chloroplasts. Meanwhile, hydrogen peroxide (H2O2) and superoxide anions showed similar trends of initially increasing at the beginning of sorus formation and decreasing in the later stages. Changes in the H2O2 content were highly significant in sorus formation. There were differences in the activity of different antioxidant enzymes in the process of sorus formation, among which superoxide dismutase (SOD) activity had a general downward trend, while ascorbate peroxidase (APX), peroxidase (POD), and catalase (CAT) showed a trend of rising in the early stages and then declining in the later stages. Moreover, POD, APX, and CAT activity had the significantly lowest levels at stage SC, SD, and SE, whereas the maximum levels of POD and APX were at stage SB, and maximum CAT levels were at stage SD. However, the malondialdehyde (MDA) content did not vary significantly during the whole development process. SOD activity gradually decreased throughout development, and the H2O2 content continued to increase, suggesting kelp sorus development may require hydrogen peroxide involvement. The activities of various antioxidant enzymes changed dynamically at different stages of sporangia development, and accurately regulated the oxygen species (ROS). The ROS increase in the process of sorus development did not harm any cells and ROS participated as a signaling molecule in the molecular regulation process of sorus development. In sorus development, the activity of RuBP carboxylase (RubisCO) initially decreased at stage SB and SC and then increased. There was no significant variation in the plant malate dehydrogenase activity. This study deepened the understanding of the hybrid kelp sorus formation process, physiological, and biochemical characteristics, and provided a theoretical basis for the artificial induction of hybrid kelp sorus formation in the future

Nasal nitric oxide in healthy Chinese children aged 6–18 years

ObjectivesTo obtain the normal values of fractional concentration of nasal nitric oxide in Chinese children aged 6–18 years, so as to provide reference for clinical diagnosis.Methods2,580 out of 3,200 children (1,359 males and 1,221 females), whom were included from 12 centers around China were taken tests, their height and weight were also recorded. Data were used to analyze the normal range and influencing factors of fractional concentration of nasal nitric oxide values.MeasurementsData was measured using the Nano Coulomb Breath Analyzer (Sunvou-CA2122, Wuxi, China), according to the American Thoracic Society/European Respiratory Society (ATS/ERS) recommendations.Main ResultsWe calculated the normal range and prediction equation of fractional concentration of nasal nitric oxide values in Chinese children aged 6–18 years. The mean FnNO values of Chinese aged 6–18 yrs was 454.5 ± 176.2 ppb, and 95% of them were in the range of 134.5–844.0 ppb. The prediction rule of FnNO values for Chinese children aged 6–11 yrs was: FnNO = 298.881 + 17.974 × age. And for children aged 12–18 yrs was: FnNO = 579.222–30.332 × (male = 0, female = 1)—5.503 × age.ConclusionsSex and age were two significant predictors of FnNO values for Chinese children(aged 12–18 yrs). Hopefully this study can provide some reference value for clinical diagnosis in children