In this study, male-specific lethal 3 homolog (Mnmsl3) was cloned and characterized from the freshwater prawn Macrobrachium nipponense (Crustacea: Decapoda: Palaemonidae) by rapid amplification of ...cDNA ends. The deduced amino acid sequences of Mnmsl3 showed high-sequence homology to the insect Msl3 and contained a conserved chromatin organization modifier domain and an MORF4-related gene domain. Real-time quantitative reverse transcription-polymerase chain reaction showed that the Mnmsl3 gene was expressed in all the investigated tissues, with the highest level of expression in the testis. The expression level of Mnmsl3 between males and females was different in the gonad (testis or ovary), abdominal ganglion, and heart. The results revealed that the Mnmsl3 gene might play roles in regulating chromatin and in dosage compensation of M. nipponense. Real-time quantitative reverse transcription-polymerase chain reaction also revealed that Mnmsl3 mRNA expression was significantly increased in both 5 and 20 days post-larvae after metamorphosis, suggesting that Mnmsl3 plays complex and important roles in the early embryonic development and sex differentiation of M. nipponense.
Magnetocaloric effect of MnV1.95Al0.05O4 was studied by the magnetization and heat capacity measurements. MnV1.95Al0.05O4 is a cubic spinel structure with ferromagnetism of second order in nature and ...performs reversible magnetic entropy around the magnetic transition temperature. The large magnetic entropy changes −ΔSM∼5.2 and 8.2J/kgK and the adiabatic temperature changes ΔTad∼1.5 and 2.6K are revealed for the magnetic field changes of 2 and 4T near the Curie temperature (TC) of 59.6K, respectively. The relative cooling power (RCP) are about 82.2 and 177.2J/kg K for magnetic field changes 2 and 4T, respectively. Compared with the parent compound, although the −ΔSM and ΔTad become smaller, the refrigeration working temperature span and the RCP have been improved.
▸ Large reversible magnetocaloric effect is studied by the magnetization and heat capacity measurements. ▸ The minimal Al substitution can improve the refrigeration working temperature span and the RCP. ▸ Candidate for magnetic refrigerant materials.
To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients.
A total of 180 ...newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform.
① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%,
=0.017) and 1p deletion (1p) (27.8%,
=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (
=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (
=1.910, 95%
1.105-3.303,
=0.020) and OS (
=2.353, 95%
1.090-5.078,
=0.029).
In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1%
40.0%,
=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months
13 months,
=0.048).
GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle.
1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.
Influence of flux pining ability in the intragrain characterized by critical current density on the harmonics AC susceptibility is studied. A sintered superconducting sample is described by ...alternating weak (intergrains or weak links) and strong (intragrains) regions, which is depicted by different critical current densities Jcw and Jcs. Simulations using the flux creep model show that with the increase of the flux pinning ability of the intragrain region, a step and two peaks in the fundamental AC susceptibility as well as more peaks in the higher order even and odd harmonics are observed. Moreover, the Coles-Coles plot of chi 3 may be used as a method to qualitatively estimate the values of Jc0s/Jc0w.
We aimed to analyze the changes of serum vascular endothelial growth factor (VEGF) before and after microwave ablation (MWA) in patients with stage IIIB-IV non-small cell lung cancer (NSCLC), and to ...observe the effects of MWA combined with chemotherapy on short-term therapeutic efficacy and long-term survival. Concentrations of serum VEGF in 20 healthy subjects were considered as controls. Changes of serum VEGF were detected by ELISA before and after MWA (1 and 7 days after treatment). Seven days after MWA, patients were divided into a combination chemotherapy group of 22 subjects and a MWA alone group of 18 subjects. Serum VEGF was measured 1 month after MWA and 4 cycles after chemotherapy (3 months) to evaluate term effects; and 1- and 2-year survival rates. Serum VEGF concentrations declined sharply 1 day after MWA, and were significantly different from the levels before treatment. Subsequently, VEGF rebounded 7 days after ablation, higher than that before treatment. At 1 and 3 months, serum VEGF levels in both treatment groups were remarkably lower than that before treatment; efficiency, or for the 1-year survival rate. However, the 2-year survival rates were significantly different between the two groups. We demonstrated that after MWA, the serum VEGF concentration undergoes a process of increasing, which might promote metastasis and recurrence of NSCLC. MWA combined with whole-body chemotherapy appears to be an effective method to increase the disease control rate, reduce the probability of metastasis and recurrence, and thus improve long-term survival.
In contrast to most amyloidogenic proteins or peptides that do not contain any significant posttranslational modifications, the prion protein (PrP) is modified with either one or two polysaccharides ...and a GPI anchor which attaches PrP to the plasma membrane. Like other amyloidogenic proteins, however, PrP adopts a fibrillar shape when converted to a disease-specific conformation. Therefore, PrP polymerization offers a unique opportunity to examine the effects of biologically relevant nonpeptidic modifications on conversion to the amyloid conformation. To test the extent to which a long hydrophobic chain at the C-terminus affects the intrinsic amyloidogenic propensity of PrP, we modified recombinant PrP with an N-myristoylamidomaleimidyl group, which can serve as a membrane anchor. We show that while this modification increases the affinity of PrP for the cell membrane, it does not alter the structure of the protein. Myristoylation of PrP affected amyloid formation in two ways: (i) it substantially decreased the extent of fibrillation, presumably due to off-pathway aggregation, and (ii) it prohibited assembly of filaments into higher order fibrils by preventing their lateral association. The negative effect on lateral association was abolished if the myristoylated moiety at the C-terminus was replaced by a polar group of similar size or by a hydrophobic group of smaller size. When preformed PrP fibrils were provided as seeds, myristoylated PrP supported fibril elongation and formation of higher order fibrils composed of several filaments. Our studies illustrate that, despite a bulky hydrophobic moiety at C-terminus, myristoylated PrP can still incorporate into fibrillar structure and that the C-terminal hydrophobic substitution does not affect the size of the proteinase K resistant core but controls the mode of lateral assembly of filaments into higher order fibrils.
Previous work (Wheeler et al, Gene Therapy 1999; 6: 271-281) has shown that plasmid DNA can be entrapped in 'stabilized plasmid-lipid particles' (SPLP) containing the fusogenic lipid ...dioleoylphosphatidylethanolamine (DOPE), low levels (5-10 mol%) of cationic lipid, and stabilized by a polyethyleneglycol (PEG) coating. The PEG moieties are attached to a ceramide anchor containing an arachidoyl acyl group (PEG-CerC20). These SPLP exhibit low transfection potencies in vitro, due in part to the long residence time of the PEG-CerC20 on the SPLP surface. In this work we employed SPLP stabilized by PEG attached to ceramide containing an octanoyl acyl group (PEG-CerC8), which is able to quickly exchange out of the SPLP, to develop systems that give rise to optimized in vitro and in vivo (regional) transfection. A particular objective was to achieve cationic lipid contents that give rise to maximum transfection levels. It is shown that by performing the dialysis procedure in the presence of increasing concentrations of citrate, SPLP containing up to 30 mol% of the cationic lipid dioleoydimethylammonium chloride (DODAC) could be generated. The SPLP produced could be isolated from empty vesicles by sucrose density gradient centrifugation, and exhibited a narrow size distribution (62 +/- 8 nm, as determined by freeze-fracture electron microscopy) and a high plasmid-to-lipid ratio of 65 microg/micromol (corresponding to one plasmid per particle) regardless of the DODAC content. It was found that isolated SPLP containing 20-24 mol% DODAC resulted in optimum transfection of COS-7 and HepG2 cells in vitro, with luciferase expression levels comparable to those achieved for plasmid DNA-cationic lipid complexes. In vivo studies employing an intraperitoneal B16 tumor model and intraperitoneal administration of SPLP also demonstrated maximum luciferase expression for DODAC contents of 20-24 mol% and significantly improved gene expression in tumor tissue as compared with complexes. We conclude that SPLP stabilized by PEG-CerC8 and containing 20-24 mol% cationic lipid are attractive alternatives to plasmid DNA-cationic lipid complexes for regional gene therapy applications.
The purpose of this study was to examine whether the prevalence of Parkinson's disease (PD) continues to rise after 80 years of age.
This is a two-stage, multi-center, cross-sectional study using a ...stratified cluster sampling approach was employed. Subjects included veterans at ≥ 60 years of age living in veterans' communities for at least one month in 18 major cities across China. In the first step, possible PD was screened using a PD screening scale. Demographic and relevant information were collected. In the second step, PD diagnosis was established using the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) diagnostic criteria.
The study was conducted during the period from December 2009 to December 2012. The study included 277 veterans' communities. Among the approached 11,593 subjects, 9676 subjects, (9096 men, 580 women) responded. The response rate was 83.46%.The age was ≥ 80 years in 6722 (69.47%) subjects. A diagnosis of PD was established in 228 subjects (2.36%) in the entire sample. The rate of PD was 2.65% in those with an age of ≥ 80 years. The rate of PD increased with increasing age (0%, 1.84%, 2.60% and 3.68% in the subjects at < 70, 70-79, 80-89 and ≥ 90 years of age, respectively; χ2 = 10.891, p = 0.001 in chi-square test). The rate of PD was higher in men (2.44%) than in women (1.46%) on the surface. However, no significant difference was detected (p = 0.241).
The prevalence of PD continues to increase beyond the age of 80 years. The prevalence of PD in Chinese veterans is not lower than that in other countries and regions.
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