Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells

The human papillomavirus (HPV) plays a central role in cervical carcinogenesis and its oncogene E7 is essential in this process. We showed here that E7 abrogated the G1 cell cycle checkpoint under hypoxia and analyzed key cell cycle related proteins for their potential role in this process. To further explore the mechanism by which E7 bypasses hypoxia-induced G1 arrest, we applied a proteomic approach and used mass spectrometry to search for proteins that are differentially expressed in E7 expressing cells under hypoxia. Among differentially expressed proteins identified, Cdc6 is a DNA replication initiation factor and exhibits oncogenic activities when overexpressed. We have recently demonstrated that Cdc6 was required for E7-induced re-replication. Significantly, here we showed that Cdc6 played a role in E7-mediated G1 checkpoint abrogation under hypoxic condition, and the function could possibly be independent from its role in DNA replication initiation. This study uncovered a new function of Cdc6 in regulating cell cycle progression and has important implications in HPV-associated cancers

Outsourcing natural resource requirements within China.

Consumption demands are final drivers for the extraction and allocation of natural resources. This paper investigates demand-driven natural resource requirements and spatial outsourcing within China in 2012 by using the latest multi-regional input-output model. Exergy is adopted as a common metric for natural resources input. The total domestic resource exergy requirements amounted to 125.5 EJ, of which the eastern area contributed the largest share of 44.5%, followed by the western area (23.9%), the central area (23.0%) and the northeastern area (8.6%). Investment was the leading final demand category, accounting for 52.9% (66.4 EJ) of national total embodied resource use (ERU). The total trade volumes of embodied resource were equivalent to 69.6% of the total direct resource input (DRI), mostly transferred from the central and western regions such as Inner Mongolia, Shanxi, Shaanxi and Xinjiang to the eastern regions such as Jiangsu, Zhejiang, Guangdong and Shanghai. The northeastern and eastern areas had physical net imports of 1213.5 PJ and 38452.6 PJ, while the central and western inland areas had physical net exports of 6364.5 PJ and 33301.5 PJ, respectively. Shanghai, Beijing, Zhejiang, Jiangsu and Guangdong had prominent ERUs which respectively were 101.6, 12.6, 11.7, 8.4 and 4.3 times of their DRIs. The ERUs of Inner Mongolia, Shaanxi, Shanxi, Ningxia and Guizhou were equal to only 17.6%, 25.3%, 27.9%, 46.0% and 50.2% of their DRIs, respectively. Regional uneven development resulted in imbalanced resource requirements across China. The findings can provide a deep understanding of China's resource-driven economic development mode, and contribute to reducing regional resource footprints and their environment outcomes under the "new normal economy"

The Double-Edges Role of Copper in the Fate of Amyloid Beta in the Presence of Anti-Oxidants

The biological fate of amyloid beta (Aβ) species is a fundamental question in Alzheimer’s disease (AD) pathogenesis. The competition between clearance and aggregation of Aβs is critical for the onset of AD. Copper has been widely considered to be an inducer of harmful crosslinking of Aβs, and an important triggering factor for the onset of AD. In this report, however, we present data to show that copper can also be an inducer of Aβ degradation in the presence of a large excess of well-known intrinsic (such as dopamine) or extrinsic (such as vitamin C) anti-oxidants. The degraded fragments were identified using SDS-Page gels, and validated via nanoLC-MS/MS. A tentative mechanism for the degradation was proposed and validated with model peptides. In addition, we performed electrophysiological analysis to investigate the synaptic functions in brain slices, and found that in the presence of a significant excess of vitamin C, Cu(II) could prevent an Aβ-induced deficit in synaptic transmission in the hippocampus. Collectively, our evidence strongly indicated that a proper combination of copper and anti-oxidants might have a positive effect on the prevention of AD. This double-edged function of copper in AD has been largely overlooked in the past. We believe that our report is very important for fully understanding the function of copper in AD pathology

Existence of Global Attractor for a 3D Brinkman-Forchheimer Equfation in Some Poincaré Unbounded Domains

In this paper, we study the existence of global attractor of a class of three-dimensional Brinkman-Forchheimer equation in some unbounded domains which satisfies Poincaré inequality. We use the tail estimation method to establish the asymptotic compactness of the solution operator and then prove the existence of the global attractor in (H01(Ω))3

Dimension Estimate of the Global Attractor for a 3D Brinkman- Forchheimer Equation

In this paper, we study the dimension estimate of global attractor for a 3D Brinkman-Forchheimer equation. Based on the differentiability of the semigroup with respect to the initial data, we show that the global attractor of strong solution of the 3D Brinkman-Forchheimer equation has finite Hausdorff and fractal dimensions

Spatial Scale Effects of the Relationship between Fractional Vegetation Coverage and Land Surface Temperature in Horqin Sandy Land, North China

Sandy range land refers to a major component of grassland area types in the semi-arid area of northern China. Monitoring of vegetation and land surface temperature (LST) using remote sensing technology can help determine the degree of desertification in a regional and/or sub regional scale, as in the Horqin Sandy Land selected in this study. Correlation analysis was performed to examine the relationship between the fractional vegetation coverage (FVC) and the LST within one growing season (from May to August 2017), at different spatial scales. The results showed that the FVC increased from 0.12 in May to 0.29 in August, and the LST increased first and then declined. The highest LST was 41.68 °C in July, while the lowest was 28.62 °C in August. At the grid scale, the LST increased first and then declined with the increase of the FVC on 25 May, 10 June, and 29 August; the FVC ranged from 0.29–0.38, 0.27–0.32, and 0.29–0.38 with the preference of the ‘turning point’, respectively. A negative correlation was identified between the FVC and the LST and without any ‘turning point’ in the fitting curve on 28 July. The correlation between FVC and LST complied with the grid scale at the sample area scale. The coupling analysis of landscape pattern expressed by FVC and LST showed that, the landscape evenness, Euclidean nearest neighbor distance, and landscape splitting degree all showed strong coupling correlation in any study period (P). The landscape aggregation of FVC and LST showed a good coupling at the relatively high and low air temperature conditions of P1 and P3. Landscape contagion showed a good coupling between FVC and LST at relatively moderate air temperature condition of P1 and P4. Air temperature conditions and characteristics of vegetation coverage should be considered for a more targeted analysis when analyzing the relationship between FVC and LST and attention should be paid to the timing and type of study area in practical application

DataSheet1_Eco-environmental quality assessment of the artificial oasis of Ningxia section of the Yellow River with the MRSEI approach.ZIP

Remote sensing ecological index (RSEI) has the advantages of rapid, repeatable and relatively accurate in regional eco-environment quality assessment. Due to the lack of consideration of the interaction of adjacent analysis units in RSEI calculation, there is a few uncertainties in the assessment results. Based on RSEI, the landscape diversity index (LDI) was introduced, which considered the heterogeneity caused by the difference between the assessment unit and the adjacent one, and rebuilt modified remote sensing ecological index (MRSEI) to evaluate the eco-environment quality in the artificial oasis of Ningxia section of Yellow River. The results showed that the area of Fair and Poor grades in the low MRSEI year (2000) was greater than that of other grades, and the area of Moderate and Fair grades was greater than that of other grades in the high MRSEI year (2020). The conversion characteristics of different grades were Poor and Fair grades to adjacent high grades. During the study period, the eco-environment quality of the study area was improved, and the composition and pattern of land use types had a significant impact on MRSEI. Introduction of LDI-improved MRSEI can not only include the heterogeneous effect between the analysis unit and the adjacent one, but also consider the spatial scale effect of LDI to make the evaluation results more credible. However, some evaluation factors of RSEI and MRSEI (e.g., LDI, NDVI, and NDBSI) represent the accumulation of surface status over long-time scales, while others (e.g., Wet and LST) reflects only short-time scale features of the land surface. Therefore, how to eliminate the uncertainty caused by temporal scale mismatch is a challenge for RSEI and MRSEI applications.</p

A 69 kb Deletion in chr19q13.42 including <i>PRPF31</i> Gene in a Chinese Family Affected with Autosomal Dominant Retinitis Pigmentosa

We aimed to identify the genetic cause of autosomal dominant retinitis pigmentosa (adRP) and characterize the underlying molecular mechanisms of incomplete penetrance in a Chinese family affected with adRP. All enrolled family members underwent ophthalmic examinations. Whole-genome sequencing (WGS), multiplex ligation-dependent probe amplification (MLPA), linkage analysis and haplotype construction were performed in all participants. RNA-seq was performed to analyze the regulating mechanism of incomplete penetrance among affected patients, mutation carriers and healthy controls. In the studied family, 14 individuals carried a novel heterozygous large deletion of 69 kilobase (kb) in 19q13.42 encompassing exon 1 of the PRPF31 gene and five upstream genes: TFPT, OSCAR, NDUFA3, TARM1, and VSTM1. Three family members were sequenced and diagnosed as non-penetrant carriers (NPCs). RNA-seq showed significant differential expression of genes in deletion between mutation carriers and healthy control. The RP11 pedigree in this study was the largest pedigree compared to other reported RP11 pedigrees with large deletions. Early onset in all affected members in this pedigree was considered to be a special phenotype and was firstly reported in a RP11 family for the first time. Differential expression of PRPF31 between affected and unaffected subjects indicates a haploinsufficiency to cause the disease in the family. The other genes with significant differential expression might play a cooperative effect on the penetrance of RP11

Screening of candidate genes at GLC3B and GLC3C loci in Chinese primary congenital glaucoma patients with targeted next generation sequencing

Primary congenital glaucoma (PCG) is characterized by developmental abnormalities of the anterior chamber angle. Although several genes have been associated with PCG, pathogenic mutations could only be detected in about 20% of Chinese patients. GLC3B (1p36.2–36.1) and GLC3C (14q24.3) loci were previously identified in PCG pedigrees via linkage analysis. However, no causative genes were reported in these loci. This study was designed to search for novel PCG-related genes in these genetic regions. DNA samples from 100 PCG patients and 200 normal controls were pooled and sequenced using a customized panel of 133 positional candidate genes located around GLC3B and GLC3C loci (±1Mb). PCG-related genes were prioritized by the distribution of variants between patients and controls. Confirmation of selected variants and co-segregation analysis were performed using Sanger sequencing. Patient and control group contained 116 and 147 rare variants respectively after screening. Three genes (ZC2HC1C, VPS13D, and PGF) were prioritized according to the distribution of variants between the two groups. Rare variants of PGF were only identified in PCG patients. To the best of our knowledge, this is the first study aiming at exploring novel PCG-related genes at GLC3B and GLC3C loci. Our preliminary results suggest that there are potential associations between ZC2HC1C, VPS13D, PGF, and PCG. However, larger cohort studies and functional assays are required to provide further evidence for the proposed genotype-phenotype association.</p

The double-edged role of copper in the fate of amyloid beta in the presence of anti-oxidants† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc01787a Click here for additional data file.

The biological fate of amyloid beta (Aβ) species is a fundamental question in Alzheimer’s disease (AD) pathogenesis. The competition between clearance and aggregation of Aβs is critical for the onset of AD. Copper has been widely considered to be an inducer of harmful crosslinking of Aβs, and an important triggering factor for the onset of AD. In this report, however, we present data to show that copper can also be an inducer of Aβ degradation in the presence of a large excess of well-known intrinsic (such as dopamine) or extrinsic (such as vitamin C) anti-oxidants. The degraded fragments were identified using SDS-Page gels, and validated via nanoLC-MS/MS. A tentative mechanism for the degradation was proposed and validated with model peptides. In addition, we performed electrophysiological analysis to investigate the synaptic functions in brain slices, and found that in the presence of a significant excess of vitamin C, Cu(ii) could prevent an Aβ-induced deficit in synaptic transmission in the hippocampus. Collectively, our evidence strongly indicated that a proper combination of copper and anti-oxidants might have a positive effect on the prevention of AD. This double-edged function of copper in AD has been largely overlooked in the past. We believe that our report is very important for fully understanding the function of copper in AD pathology