Chemical characterization of PM2.5 from a southern coastal city of China:applications of modeling and chemical tracers in demonstrationof regional transport

An intensive sampling campaign of airborne fine particles (PM2.5) was conducted at Sanya, a coastal city in Southern China, from January to February 2012. Chemical analyses and mass reconstruction were used identify potential pollution sources and investigate atmospheric reaction mechanisms. A thermodynamic model indicated that low ammonia and high relative humidity caused the aerosols be acidic and that drove heterogeneous reactions which led to the formation of secondary inorganic aerosol. Relationships among neutralization ratios, free acidity, and air-mass trajectories suggest that the atmosphere at Sanya was impacted by both local and regional emissions. Three major transport pathways were identified, and flow from the northeast (from South China) typically brought the most polluted air to Sanya. A case study confirmed strong impact from South China (e.g., Pearl River Delta region) (contributed 76.8% to EC, and then this result can be extended to primary pollutants) when the northeast winds were dominant. The Weather Research Forecasting Black carbon model and trace organic markers were used to apportion local pollution versus regional contributions. Results of the study offer new insights into the atmospheric conditions and air pollution at this coastal city

The S phase checkpoint promotes the Smc5/6 complex dependent SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε

Replication fork stalling and accumulation of single-stranded DNA trigger the S phase checkpoint, a signalling cascade that, in budding yeast, leads to the activation of the Rad53 kinase. Rad53 is essential in maintaining cell viability, but its targets of regulation are still partially unknown. Here we show that Rad53 drives the hyper-SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε, principally following replication forks stalling induced by nucleotide depletion. Pol2 is the main target of SUMOylation within the replisome and its modification requires the SUMO-ligase Mms21, a subunit of the Smc5/6 complex. Moreover, the Smc5/6 complex co-purifies with Pol ε, independently of other replisome components. Finally, we map Pol2 SUMOylation to a single site within the N-terminal catalytic domain and identify a SUMO-interacting motif at the C-terminus of Pol2. These data suggest that the S phase checkpoint regulate Pol ε during replication stress through Pol2 SUMOylation and SUMO-binding abilit

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

Citation: Shi, Z. Z., Chapes, S. K., Ben-Arieh, D., & Wu, C. H. (2016). An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data. Plos One, 11(8), 39. doi:10.1371/journal.pone.0161131We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as "sepsis". Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-a ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies

Highway increases concentrations of toxic metals in giant panda habitat

The Qinling panda subspecies (Ailuropoda melanoleuca qinlingensis) is highly endangered with fewer than 350 individuals inhabiting the Qinling Mountains. Previous studies have indicated that giant pandas are exposed to heavy metals, and a possible source is vehicle emission. The concentrations of Cu, Zn, Mn, Pb, Cr, Ni, Cd, Hg, and As in soil samples collected from sites along a major highway bisecting the panda's habitat were analyzed to investigate whether the highway was an important source of metal contamination. There were 11 sites along a 30-km stretch of the 108th National Highway, and at each site, soil samples were taken at four distances from the highway (0, 50, 100, and 300 m) and at three soil depths (0, 5, 10 cm). Concentrations of all metals except As exceeded background levels, and concentrations of Cu, Zn, Mn, Pb, and Cd decreased significantly with increasing distance from the highway. Geo-accumulation index indicated that topsoil next to the highway was moderately contaminated with Pb and Zn, whereas topsoil up to 300 m away from the highway was extremely contaminated with Cd. The potential ecological risk index demonstrated that this area was in a high degree of ecological hazards, which were also due to serious Cd contamination. And, the hazard quotient indicated that Cd, Pb, and Mn especially Cd could pose the health risk to giant pandas. Multivariate analyses demonstrated that the highway was the main source of Cd, Pb, and Zn and also put some influence on Mn. The study has confirmed that traffic does contaminate roadside soils and poses a potential threat to the health of pandas. This should not be ignored when the conservation and management of pandas is considered

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Disease Burden, Risk Factors, and Temporal Trends in Breast Cancer in Low‐ and Middle‐Income Countries: A Global Study

Introduction: Breast cancer poses significant health risks to women and strains healthcare systems extensively. In low‐ and middle‐income countries (LMICs), limited resources and inadequate healthcare infrastructures further exacerbate the challenges of breast cancer prevention, treatment, and awareness. Methods: We examined the prevalence, risk factors, and trends of breast cancer in LMICs. Data on disability‐adjusted life years (DALYs) and breast cancer risk factors were extracted from the Global Burden of Disease (GBD) databases for 203 countries or territories from 1990 to 2019. LMIC DALY rates were examined using joinpoint regression analysis. Results: Among the income groups, the lower middle‐income category had the highest DALYs value, with 1787 years per 100,000 people. LMICs collectively accounted for 74% of the global burden of DALYs lost due to breast cancer in 2019. However, it remained relatively consistent in lower middle income countries (LMCs). In LMCs, the risk associated with metabolic syndromes was higher compared to that with behavioral factors alone. For the past three decades, breast cancer incidences increased significantly in LMCs (average annual percent change [AAPC]: 1.212, confidence intervals [CI]: 1.51–1.87, p < 0.001), upper middle income countries (AAPC: 1.701, CI: 1.12–1.48, p < 0.001), and low‐income countries (AAPC: 1.002, CI: 1.57–1.68, p < 0.001). Conclusion: This research shows how breast cancer in LMICs is aggravated by low resources and healthcare infrastructure. To effectively combat breast cancer in these areas, future strategies must prioritize improvements in healthcare infrastructure, awareness campaigns, and early detection mechanisms

Application of Flexible Bronchoscopy in Inhalation Lung Injury

Background: As acute inhalational injury is an uncommon presentation to most institutions, a standard approach to its assessment and management, especially using flexible bronchoscopy, has not received significant attention. Methods: The objective of this study is to evaluate the value of using flexible bronchoscopy as part of the evaluation and management of patients with inhalational lung injury. Twenty-three cases of inhalational lung injury were treated in our three hospitals after a fire in a residential building. The twenty cases that underwent bronchoscopy as part of their management are included in this analysis. After admission, the first bronchoscopy was conducted within 18-72 hours post inhalational injury. G2-level patients were reexamined 24 hours after the first bronchoscopy, while G1-level patients were reexamined 72 hours later. Subsequently, all patients were re-examined every 2-3 days until recovered or until only tunica mucosa bronchi congestion was identified by bronchoscopy. Results: Twenty patients had airway injury diagnosed by bronchoscopy including burns to the larynx and glottis or large airways. Bronchoscopic classification of the inhalation injury was performed, identifying 12 cases of grade G1 changes and 8 cases of grade G2. The airway injury in the 12 cases of grade G1 patients demonstrated recovery in 2-8 days, in the airway injury of the 8 cases of grade G2 patients had a prolonged recovery with airway injury improving in 6-21 days averaged. The difference in recovery time between the two groups was significant (P Conclusions: The use of flexible bronchoscopy has great value in the diagnosis of inhalational injury without any complications. Its use should be incorporated into clinical practice

Sex Differential Genetic Effect of Chromosome 9p21 on Subclinical Atherosclerosis

BACKGROUND: Chromosome 9p21 has recently been shown to be a risk region for a broad range of vascular diseases. Since carotid intima-media thickness (IMT) and plaque are independent predictors for vascular diseases, the association between 9p21 and these two phenotypes was investigated. METHODOLOGY/PRINCIPAL FINDINGS: Carotid segment-specific IMT and plaques were obtained in 1083 stroke- and myocardial infarction-free volunteers. We tested the genotypes and haplotypes of key single nucleotide polymorphisms (SNPs) on chromosome 9p21 for the associations with carotid IMT and plaque. Multivariate permutation analyses demonstrated that carriers of the T allele of SNP rs1333040 were significantly associated with thicker common carotid artery (CCA) IMT (p=0.021) and internal carotid artery (ICA) IMT (p=0.033). The risk G allele of SNP rs2383207 was associated with ICA IMT (p=0.007). Carriers of the C allele of SNP rs1333049 were found to be significantly associated with thicker ICA IMT (p=0.010) and the greater risk for the presence of carotid plaque (OR=1.57 for heterozygous carriers; OR=1.75 for homozygous carriers). Haplotype analysis showed a global p value of 0.031 for ICA IMT and 0.115 for the presence of carotid plaque. Comparing with the other haplotypes, the risk TGC haplotype yielded an adjusted p value of 0.011 and 0.017 for thicker ICA IMT and the presence of carotid plaque respectively. Further analyzing the data separated by sex, the results were significant only in men but not in women. CONCLUSIONS: Chromosome 9p21 had a significant association with carotid atherosclerosis, especially ICA IMT. Furthermore, such genetic effect was in a gender-specific manner in the Han Chinese population

Fine Mapping of the NRG1 Hirschsprung's Disease Locus

The primary pathology of Hirschsprung's disease (HSCR, colon aganglionosis) is the absence of ganglia in variable lengths of the hindgut, resulting in functional obstruction. HSCR is attributed to a failure of migration of the enteric ganglion precursors along the developing gut. RET is a key regulator of the development of the enteric nervous system (ENS) and the major HSCR-causing gene. Yet the reduced penetrance of RET DNA HSCR-associated variants together with the phenotypic variability suggest the involvement of additional genes in the disease. Through a genome-wide association study, we uncovered a ∼350 kb HSCR-associated region encompassing part of the neuregulin-1 gene (NRG1). To identify the causal NRG1 variants contributing to HSCR, we genotyped 243 SNPs variants on 343 ethnic Chinese HSCR patients and 359 controls. Genotype analysis coupled with imputation narrowed down the HSCR-associated region to 21 kb, with four of the most associated SNPs (rs10088313, rs10094655, rs4624987, and rs3884552) mapping to the NRG1 promoter. We investigated whether there was correlation between the genotype at the rs10088313 locus and the amount of NRG1 expressed in human gut tissues (40 patients and 21 controls) and found differences in expression as a function of genotype. We also found significant differences in NRG1 expression levels between diseased and control individuals bearing the same rs10088313 risk genotype. This indicates that the effects of NRG1 common variants are likely to depend on other alleles or epigenetic factors present in the patients and would account for the variability in the genetic predisposition to HSCR