Natural Variability in Projections of Climate Change Impacts on Fine Particulate Matter Pollution

Variations in meteorology associated with climate change can impact fine particulate matter (PM2.5) pollution by affecting natural emissions, atmospheric chemistry, and pollutant transport. However, substantial discrepancies exist among model-based projections of PM2.5 impacts driven by anthropogenic climate change. Natural variability can significantly contribute to the uncertainty in these estimates. Using a large ensemble of climate and atmospheric chemistry simulations, we evaluate the influence of natural variability on projections of climate change impacts on PM2.5 pollution in the United States. We find that natural variability in simulated PM2.5 can be comparable or larger than reported estimates of anthropogenic-induced climate impacts. Relative to mean concentrations, the variability in projected PM2.5 climate impacts can also exceed that of ozone impacts. Based on our projections, we recommend that analyses aiming to isolate the effect climate change on PM2.5 use 10 years or more of modeling to capture the internal variability in air quality and increase confidence that the anthropogenic-forced effect is differentiated from the noise introduced by natural variability. Projections at a regional scale or under greenhouse gas mitigation scenarios can require additional modeling to attribute impacts to climate change. Adequately considering natural variability can be an important step toward explaining the inconsistencies in estimates of climate-induced impacts on PM2.5. Improved treatment of natural variability through extended modeling lengths or initial condition ensembles can reduce uncertainty in air quality projections and improve assessments of climate policy risks and benefits

A three dimensional model of the photosynthetic membranes of Ectothiorhodospira halochloris

The three dimensional organization of the complete photosynthetic apparatus of the extremely halophilic, bacteriochlorophyll b containing Ectothiorhodospira halochloris has been elaborated by several techniques of electron microscopy. Essentially all thylakoidal sacs are disc shaped and connected to the cytoplasmic membrane by small membraneous ldquobridgesrdquo. In sum, the lumina of all thylakoids (intrathylakoidal space) form one common periplasmic space. Thin sections confirm a paracrystalline arrangement of the photosynthetic complexes in situ. The ontogenic development of the photosynthetic apparatus is discussed based on a structural model derived from serial thin sections

Surface topography of hydroxyapatite affects ROS17/2.8 cells response

Hydroxyapatite (HA) has been used in orthopedic, dental, and maxillofacial surgery as a bone substitute. The aim of this investigation was to study the effect of surface topography produced by the presence of microporosity on cell response, evaluating: cell attachment, cell morphology, cell proliferation, total protein content, and alkaline phosphatase (ALP) activity. HA discs with different percentages of microporosity (< 5%, 15%, and 30%) were confected by means of the combination of uniaxial powder pressing and different sintering conditions. ROS17/2.8 cells were cultured on HA discs. For the evaluation of attachment, cells were cultured for two hours. Cell morphology was evaluated after seven days. After seven and fourteen days, cell proliferation, total protein content, and ALP activity were measured. Data were compared by means of ANOVA and Duncan’s multiple range test, when appropriate. Cell attachment (p = 0.11) and total protein content (p = 0.31) were not affected by surface topography. Proliferation after 7 and 14 days (p = 0.0007 and p = 0.003, respectively), and ALP activity (p = 0.0007) were both significantly decreased by the most irregular surface (HA30). These results suggest that initial cell events were not affected by surface topography, while surfaces with more regular topography, as those present in HA with 15% or less of microporosity, favored intermediary and final events such as cell proliferation and ALP activity

Mutation analysis of cell-free DNA and single circulating tumor cells in metastatic breast cancer patients with high CTC counts

Purpose: The purpose of this study was to directly compare mutation profiles in multiple single CTCs and cfDNA isolated from the same blood samples taken from patients with metastaic breast cancer (MBC). We aimed to determine whether cell-free DNA would reflect the heterogeneity observed in 40 single CTCs. Experimental design: CTCs were enumerated by Cellsearch. CTC count was compared with the quantity of matched cfDNA and serum CA15-3 and alkaline phosphatase (ALP) in 112 patients with metastatic breast cancer. In 5 patients with {greater than or equal to}100 CTCs, multiple individual EpCAM-positive CTCs were isolated by DEPArray and compared with matched cfDNA and primary tumour tissue by targeted next generation sequencing (NGS) of ~2200 mutations in 50 cancer genes. Results: In the whole cohort, total cfDNA levels and cell counts ({greater than or equal to}5 CTCs) were both significantly associated with overall survival, unlike CA15-3 and ALP. NGS analysis of 40 individual EpCAM-positive CTCs from 5 patients with MBC revealed mutational heterogeneity in PIK3CA, TP53, ESR1 and KRAS genes between individual CTCs. In all 5 patients cfDNA profiles provided an accurate reflection of mutations seen in individual CTCs. ESR1 and KRAS gene mutations were absent from primary tumour tissue and therefore likely reflect either a minor sub-clonal mutation or were acquired with disease progression. Conclusion: Our results demonstrate that cfDNA reflects persisting EpCAM-positive CTCs in patients with high CTC counts and therefore may enable monitoring of the metastatic burden for clinical decision-making. Experimental Design: DNA methylation was investigated in independent tumor cohorts using Illumina HumanMethylation arrays and gene expression by Affymetrix arrays and qRT-PCR. The role of Msh homeobox 1 (MSX1) in drug sensitivity was investigated by gene reintroduction and siRNA knockdown of ovarian cancer cell lines. Results: CpG sites at contiguous genomic locations within the MSX1 gene have significantly lower levels of methylation in independent cohorts of HGSOC patients, which recur by 6 months compared with after 12 months (P < 0.05, q < 0.05, n = 78), have poor RECIST response (P < 0.05, q < 0.05, n = 61), and are associated with PFS in an independent cohort (n = 146). A decrease in methylation at these CpG sites correlates with decreased MSX1 gene expression. MSX1 expression is associated with PFS (HR, 0.92; 95% CI, 0.85–0.99; P = 0.029; n = 309). Cisplatin-resistant ovarian cancer cell lines have reduced MSX1 expression, and MSX1 overexpression leads to cisplatin sensitization, increased apoptosis, and increased cisplatin-induced p21 expression. Conclusions: Hypomethylation of CpG sites within the MSX1 gene is associated with resistant HGSOC disease at presentation and identifies expression of MSX1 as conferring platinum drug sensitivity

Extraparenchymal neurocysticercosis in the United States: a case report

<p>Abstract</p> <p>Introduction</p> <p>Neurocysticercosis is endemic in the developing world, but is becoming more common in the United States due to immigration.</p> <p>Case presentation</p> <p>A 26-year-old Caucasian man presented with headache, nausea and vomiting and was found to have hydrocephalus and meningitis. Brain imaging and immunological studies were suggestive of neurocysticercosis. Endoscopic removal of the cyst resulted in resolution of symptoms. This case represents a combination of two rare presentations of extraparenchymal neurocysticercosis; intraventricular neurocysticercosis and subarachnoid neurocysticercosis.</p> <p>Conclusion</p> <p>Although neurocysticercosis is pleomorphic in its presentation, extraparenchymal neurocysticercosis may be challenging to diagnose and treat. Clinicians should be aware of this condition given increasing incidence in the United States.</p

Understanding the threats posed by non-native species: public vs. conservation managers.

Public perception is a key factor influencing current conservation policy. Therefore, it is important to determine the influence of the public, end-users and scientists on the prioritisation of conservation issues and the direct implications for policy makers. Here, we assessed public attitudes and the perception of conservation managers to five non-native species in the UK, with these supplemented by those of an ecosystem user, freshwater anglers. We found that threat perception was not influenced by the volume of scientific research or by the actual threats posed by the specific non-native species. Media interest also reflected public perception and vice versa. Anglers were most concerned with perceived threats to their recreational activities but their concerns did not correspond to the greatest demonstrated ecological threat. The perception of conservation managers was an amalgamation of public and angler opinions but was mismatched to quantified ecological risks of the species. As this suggests that invasive species management in the UK is vulnerable to a knowledge gap, researchers must consider the intrinsic characteristics of their study species to determine whether raising public perception will be effective. The case study of the topmouth gudgeon Pseudorasbora parva reveals that media pressure and political debate has greater capacity to ignite policy changes and impact studies on non-native species than scientific evidence alone

Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors

Bacterial protein synthesis is intricately connected to metabolic rate. One of the ways in which bacteria respond to environmental stress is through posttranslational modifications of translation factors. Translation elongation factor Tu (EF-Tu) is methylated and phosphorylated in response to nutrient starvation upon entering stationary phase, and its phosphorylation is a crucial step in the pathway toward sporulation. We analyze how phosphorylation leads to inactivation of Escherichia coli EF-Tu. We provide structural and biophysical evidence that phosphorylation of EF-Tu at T382 acts as an efficient switch that turns off protein synthesis by decoupling nucleotide binding from the EF-Tu conformational cycle. Direct modifications of the EF-Tu switch I region or modifications in other regions stabilizing the β-hairpin state of switch I result in an effective allosteric trap that restricts the normal dynamics of EF-Tu and enables the evasion of the control exerted by nucleotides on G proteins. These results highlight stabilization of a phosphorylation-induced conformational trap as an essential mechanism for phosphoregulation of bacterial translation and metabolism. We propose that this mechanism may lead to the multisite phosphorylation state observed during dormancy and stationary phase

No Association between HIV and Intimate Partner Violence among Women in 10 Developing Countries

Intimate Partner Violence (IPV) has been reported to be a determinant of women's risk for HIV. We examined the relationship between women's self-reported experiences of IPV in their most recent relationship and their laboratory-confirmed HIV serostatus in ten low- to middle-income countries.Data for the study came from the most recent Demographic and Health Surveys conducted in Dominican Republic, Haiti, India, Kenya, Liberia, Malawi, Mali, Rwanda, Zambia and Zimbabwe. Each survey population was a cross-sectional sample of women aged 15-49 years. Information on IPV was obtained by a face-to-face interview with the mother with an 81.1% response rate; information on HIV serostatus was obtained from blood samples with an 85.3% response rate. Demographic and socioeconomic variables were considered as potentially confounding covariates. Logistic regression models accounting for multi-stage survey design were estimated individually for each country and as a pooled total with country fixed effects (n = 60,114). Country-specific adjusted odds ratios (OR) for physical or sexual IPV compared to neither ranged from 0.45 [95% confidence interval (CI): 0.23-0.90] in Haiti to 1.35 [95% CI: 0.95-1.90] in India; the pooled association was 1.03 [95% CI: 0.94-1.13]. Country-specific adjusted ORs for physical and sexual IPV compared to no sexual IPV ranged from 0.41 [95% CI: 0.12-1.36] in Haiti to 1.41 [95% CI: 0.26-7.77] in Mali; the pooled association was 1.05 [95% CI: 0.90-1.22].IPV and HIV were not found to be consistently associated amongst ever-married women in national population samples in these lower income countries, suggesting that IPV is not consistently associated with HIV prevalence worldwide. More research is needed to understand the circumstances in which IPV and HIV are and are not associated with one another