Multiaxial Fatigue Analysis of Connecting Bolt at High-Speed Train Axle Box under Structural Subharmonic Resonance.

Based on the dynamic characteristics of the axle box front cover of high-speed trains in the subharmonic resonance state, the nonlinear single-degree-of-freedom (SDOF) model was proved to be reasonable, and reasons for the ineffectiveness of the common prevention methods for preventing bolt failure were analyzed firstly. Then, dynamic stress of the bolt was simulated by innovatively adopting the linear method based on frequency response analysis. The stress simulation method was verified to be practical under the subharmonic resonance state by analyzing and comparing the experimental and numerical results of the bolted front cover. It was proved that the linear method was accurate enough to simulate the dynamic stress of bolts, which is of great engineering significance. In addition to the transverse resonance stress of bolts caused by drastic vertical vibration of the front cover, the tensile resonance stress at the root of the first engaged thread was too large to be neglected on account of the first-order bending modes of bolts. Next, equivalent stress amplitude of the multiaxial stresses was obtained by means of the octahedral shear stress criterion. Finally, fatigue life of bolts was predicted in terms of S-N curve suitable for bolt fatigue life analysis. It argued that the bolts were prone to multiaxial fatigue failure when the front cover was in subharmonic resonance for more than 26.8 h, and the fatigue life of bolts could be greatly improved when the wheel polygonization was eliminated by shortening the wheel reprofiling interval.

Impaired maturation of large dense-core vesicles in muted-deficient adrenal chromaffin cells.

The large dense-core vesicle (LDCV), a type of lysosome-related organelle, is involved in the secretion of hormones and neuropeptides in specialized secretory cells. The granin family is a driving force in LDCV biogenesis, but the machinery for granin sorting to this biogenesis pathway is largely unknown. The mu mutant mouse, which carries a spontaneous null mutation on the Muted gene (also known as Bloc1s5), which encodes a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), is a mouse model of Hermansky-Pudlak syndrome. Here, we found that LDCVs were enlarged in mu adrenal chromaffin cells. Chromogranin A (CgA, also known as CHGA) was increased in mu adrenals and muted-knockdown cells. The increased CgA in mu mice was likely due a failure to export this molecule out of immature LDCVs, which impairs LDCV maturation and docking. In mu chromaffin cells, the size of readily releasable pool and the vesicle release frequency were reduced. Our studies suggest that the muted protein is involved in the selective export of CgA during the biogenesis of LDCVs.

Dysbindin-1C is required for the survival of hilar mossy cells and the maturation of adult newborn neurons in dentate gyrus.

DTNBP1 (dystrobrevin-binding protein 1), which encodes dysbindin-1, is one of the leading susceptibility genes for schizophrenia. Both dysbindin-1B and -1C isoforms are decreased, but the dysbindin-1A isoform is unchanged in schizophrenic hippocampal formation, suggesting dysbindin-1 isoforms may have distinct roles in schizophrenia. We found that mouse dysbindin-1C, but not dysbindin-1A, is localized in the hilar glutamatergic mossy cells of the dentate gyrus. The maturation rate of newborn neurons in sandy (sdy) mice, in which both dysbindin-1A and -1C are deleted, is significantly delayed when compared with that in wild-type mice or with that in muted (mu) mice in which dysbindin-1A is destabilized but dysbindin-1C is unaltered. Dysbindin-1C deficiency leads to a decrease in mossy cells, which causes the delayed maturation of newborn neurons. This suggests that dysbindin-1C, rather than dysbindin-1A, regulates adult hippocampal neurogenesis in a non-cell autonomous manner.

The BLOS1-interacting protein KXD1 is involved in the biogenesis of lysosome-related organelles.

Biogenesis of lysosome-related organelles (LROs) complex-1 (BLOC-1) is an eight-subunit complex involved in lysosomal trafficking. Interacting proteins of these subunits expand the understanding of its biological functions. With the implementation of the naïve Bayesian analysis, we found that a human uncharacterized 20 kDa coiled-coil KxDL protein, KXD1, is a BLOS1-interacting protein. In vitro binding assays confirmed the interaction between BLOS1 and KXD1. The mouse KXD1 homolog was widely expressed and absent in Kxd1 knockout (KO) mice. BLOS1 was apparently reduced in Kxd1-KO mice. Mild defects in the melanosomes of the retinal pigment epithelia and in the platelet dense granules of the Kxd1-KO mouse were observed, mimicking a mouse model of mild Hermansky-Pudlak syndrome that affects the biogenesis of LROs.

Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report.

Turner syndrome (TS) is a congenital chromosomal abnormality that affects approximately 1 in 2,500 people. Both in China and abroad, few studies exist on the incidence of tumors in patients with TS. Most reported cases are complicated with gonadal germ cell tumors, and extragonadal tumors are rare, with the latter not yet being reported in China. Through chromosome karyotype analysis and surgical exploration, a pediatric patent was diagnosed with TS complicated with gonadoblastoma and adrenal neuroblastoma. The patient was short in stature and had a facial deformity. After admission, adrenal computed tomography was conducted, and a right adrenal mass was identified as a neurogenic tumor. After surgical resection and gonadal exploration, the pathological results revealed left gonadoblastoma, right gonadal stromal cell hyperplasia, and ganglion neuroblastoma (mixed type) in the right adrenal gland. Pediatric patients with TS have an increased likelihood of developing neuroblastoma and adrenal-related tumors, and changes in adrenal hormone levels and clinical manifestations are often not obvious when combined with adrenal-related tumors. To avoid missed diagnosis and delayed treatment, screening for adrenal tumors is therefore recommended for patients with TS before the initiation of growth hormone treatment.

Dysbindin deficiency in sandy mice causes reduction of snapin and displays behaviors related to schizophrenia.

Schizophrenia (SCZ) is a complex trait with a high heritability. The DTNBP1 gene (encoding dysbindin) is one of the leading susceptible genes of SCZ. This risk gene has been reported to be associated with clinical symptoms such as negative symptoms and cognitive deficits. Although reduction of dysbindin expression in schizophrenic brain tissue has been reported, how this contributes to its symptomatology remains uncertain. The sandy (sdy) mouse, which harbors a spontaneously occurring deletion in the Dtnbp1 gene and expresses no dysbindin protein, provides a unique tool to study the role of dysbindin in SCZ. Our recent findings reveal that the sdy mice exhibit specific defects of neurosecretion and synaptic morphology in hippocampal neurons. We here further described that sdy manifested schizophrenia-like behaviors such as social withdrawal and cognitive deficits. In sdy hippocampus, the steady-state level of snapin (a SNAP25-binding protein and a synaptic priming regulator) was reduced due to loss of dysbindin. We further characterized that a 30-residue peptide in dysbindin (90-119 amino acids) mediated the interaction with snapin. Our results suggest that the destabilization of snapin in sdy mice may lead to abnormal neurotransmission and therefore abnormal behaviors. This further defines the sdy mutant as a potential model in schizophrenia research.

Epidemiological characteristics of foodborne diseases among primary and secondary school students in Maanshan City / 中国学校卫生

Objective@#This study analyzed the active surveillance data of foodborne diseases among primary and secondary school students in Maanshan City. The purpose is to explore its epidemiological characteristics and provide evidence for effective prevention and control measures.@*Methods@#Descriptive epidemiological method was used to analyze 976 cases of primary and secondary school students collected at the sentinel hospital in Maanshan City. Chi-square test was used to compare the distribution of foodborne diseases among primary and secondary school students with different characteristics, and the Logistic regression analysis was conducted on the influencing factors timely rate of health-seeking.@*Results@#There were statistically significant differences in the distribution of food-borne diseases among primary and secondary school students in gender, urban and rural areas, hospital grades, administrative areas, eating places and food packaging or processing methods ( χ 2=5.24, 6.86, 41.45, 48.09, 27.87, 23.62, P < 0.05 ). There were 624 males (66.78%) and 352 females (33.22%). July-October was the peak period of health-seeking ( 45.77 %), and Huashan District (31.45%) had the largest number of cases. Multivariate Logistic regression showed that women ( OR =1.36, 95% CI =1.04-1.79), summer ( OR =1.68, 95% CI =1.19-2.35), autumn ( OR =1.49, 95% CI =1.04-2.12) and the Hexian area ( OR =2.71, 95% CI =1.77-4.15) were positively correlated with the timeliness of health-seeking.@*Conclusion@#The cases of foodborne diseases in primary and secondary schools in Maanshan City were mainly male. Summer and autumn were the main onset times. Huashan District was the key prevention county. It is suggested that all departments should take active and effective measures to strengthen the prevention and control of foodborne diseases among primary and secondary school students.

DTNBP1, a schizophrenia susceptibility gene, affects kinetics of transmitter release.

Schizophrenia is one of the most debilitating neuropsychiatric disorders, affecting 0.5-1.0% of the population worldwide. Its pathology, attributed to defects in synaptic transmission, remains elusive. The dystrobrevin-binding protein 1 (DTNBP1) gene, which encodes a coiled-coil protein, dysbindin, is a major susceptibility gene for schizophrenia. Our previous results have demonstrated that the sandy (sdy) mouse harbors a spontaneously occurring deletion in the DTNBP1 gene and expresses no dysbindin protein (Li, W., Q. Zhang, N. Oiso, E.K. Novak, R. Gautam, E.P. O'Brien, C.L. Tinsley, D.J. Blake, R.A. Spritz, N.G. Copeland, et al. 2003. Nat. Genet. 35:84-89). Here, using amperometry, whole-cell patch clamping, and electron microscopy techniques, we discovered specific defects in neurosecretion and vesicular morphology in neuroendocrine cells and hippocampal synapses at the single vesicle level in sdy mice. These defects include larger vesicle size, slower quantal vesicle release, lower release probability, and smaller total population of the readily releasable vesicle pool. These findings suggest that dysbindin functions to regulate exocytosis and vesicle biogenesis in endocrine cells and neurons. Our work also suggests a possible mechanism in the pathogenesis of schizophrenia at the synaptic level.

The BLOC interactomes form a network in endosomal transport.

With the identification of more than a dozen novel Hermansky-Pudlak Syndrome (HPS) proteins in vesicle trafficking in higher eukaryotes, a new class of trafficking pathways has been described. It mainly consists of three newly-defined protein complexes, BLOC-1, -2, and -3. Compelling evidence indicates that these complexes together with two other well-known complexes, AP3 and HOPS, play important roles in endosomal transport. The interactions between these complexes form a network in protein trafficking via endosomes and cytoskeleton. Each node of this network has intra-complex and extra-complex interactions. These complexes are connected by direct interactions between the subunits from different complexes or by indirect interactions through coupling nodes that interact with two or more subunits from different complexes. The dissection of this network facilitates the understanding of a dynamic but elaborate transport machinery in protein/membrane trafficking. The disruption of this network may lead to abnormal trafficking or defective organellar development as described in patients with Hermansky-Pudlak syndrome.