Neutralization activity in a geographically diverse East London cohort of human immunodeficiency virus type 1-infected patients: clade C infection results in a stronger and broader humoral immune response than clade B infection.

The array of human immunodeficiency virus (HIV) subtypes encountered in East London, an area long associated with migration, is unusually heterogeneous, reflecting the diverse geographical origins of the population. In this study it was shown that viral subtypes or clades infecting a sample of HIV type 1 (HIV-1)-positive individuals in East London reflect the global pandemic. The authors studied the humoral response in 210 treatment-naïve chronically HIV-1-infected (>1 year) adult subjects against a panel of 12 viruses from six different clades. Plasmas from individuals infected with clade C, but also plasmas from clade A, and to a lesser degree clade CRF02_AG and CRF01_AE, were significantly more potent at neutralizing the tested viruses compared with plasmas from individuals infected with clade B. The difference in humoral robustness between clade C- and B-infected patients was confirmed in titration studies with an extended panel of clade B and C viruses. These results support the approach to develop an HIV-1 vaccine that includes clade C or A envelope protein (Env) immunogens for the induction of a potent neutralizing humoral response.

Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA.

Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer cells in response to three distinct tumor microenvironmental stresses: lactic acidosis, glucose deprivation, and hypoxia. We found that lactic acidosis and glucose deprivation trigger highly similar transcriptional responses, each inducing features of starvation response. In contrast to their comparable effects on gene expression, lactic acidosis and glucose deprivation have opposing effects on glucose uptake. This divergence of metabolic responses in the context of highly similar transcriptional responses allows the identification of a small subset of genes that are regulated in opposite directions by these two conditions. Among these selected genes, TXNIP and its paralogue ARRDC4 are both induced under lactic acidosis and repressed with glucose deprivation. This induction of TXNIP under lactic acidosis is caused by the activation of the glucose-sensing helix-loop-helix transcriptional complex MondoA:Mlx, which is usually triggered upon glucose exposure. Therefore, the upregulation of TXNIP significantly contributes to inhibition of tumor glycolytic phenotypes under lactic acidosis. Expression levels of TXNIP and ARRDC4 in human cancers are also highly correlated with predicted lactic acidosis pathway activities and associated with favorable clinical outcomes. Lactic acidosis triggers features of starvation response while activating the glucose-sensing MondoA-TXNIP pathways and contributing to the "anti-Warburg" metabolic effects and anti-tumor properties of cancer cells. These results stem from integrative analysis of transcriptome and metabolic response data under various tumor microenvironmental stresses and open new paths to explore how these stresses influence phenotypic and metabolic adaptations in human cancers.

Gold mining in the Peruvian Amazon: global prices, deforestation, and mercury imports.

Many factors such as poverty, ineffective institutions and environmental regulations may prevent developing countries from managing how natural resources are extracted to meet a strong market demand. Extraction for some resources has reached such proportions that evidence is measurable from space. We present recent evidence of the global demand for a single commodity and the ecosystem destruction resulting from commodity extraction, recorded by satellites for one of the most biodiverse areas of the world. We find that since 2003, recent mining deforestation in Madre de Dios, Peru is increasing nonlinearly alongside a constant annual rate of increase in international gold price (∼18%/yr). We detect that the new pattern of mining deforestation (1915 ha/year, 2006-2009) is outpacing that of nearby settlement deforestation. We show that gold price is linked with exponential increases in Peruvian national mercury imports over time (R(2) = 0.93, p = 0.04, 2003-2009). Given the past rates of increase we predict that mercury imports may more than double for 2011 (∼500 t/year). Virtually all of Peru's mercury imports are used in artisanal gold mining. Much of the mining increase is unregulated/artisanal in nature, lacking environmental impact analysis or miner education. As a result, large quantities of mercury are being released into the atmosphere, sediments and waterways. Other developing countries endowed with gold deposits are likely experiencing similar environmental destruction in response to recent record high gold prices. The increasing availability of satellite imagery ought to evoke further studies linking economic variables with land use and cover changes on the ground.

Hostile attributional bias and aggressive behavior in global context.

We tested a model that children's tendency to attribute hostile intent to others in response to provocation is a key psychological process that statistically accounts for individual differences in reactive aggressive behavior and that this mechanism contributes to global group differences in children's chronic aggressive behavior problems. Participants were 1,299 children (mean age at year 1 = 8.3 y; 51% girls) from 12 diverse ecological-context groups in nine countries worldwide, followed across 4 y. In year 3, each child was presented with each of 10 hypothetical vignettes depicting an ambiguous provocation toward the child and was asked to attribute the likely intent of the provocateur (coded as benign or hostile) and to predict his or her own behavioral response (coded as nonaggression or reactive aggression). Mothers and children independently rated the child's chronic aggressive behavior problems in years 2, 3, and 4. In every ecological group, in those situations in which a child attributed hostile intent to a peer, that child was more likely to report that he or she would respond with reactive aggression than in situations when that same child attributed benign intent. Across children, hostile attributional bias scores predicted higher mother- and child-rated chronic aggressive behavior problems, even controlling for prior aggression. Ecological group differences in the tendency for children to attribute hostile intent statistically accounted for a significant portion of group differences in chronic aggressive behavior problems. The findings suggest a psychological mechanism for group differences in aggressive behavior and point to potential interventions to reduce aggressive behavior.

Fearonomics and the Role of Nigeria's Private Sector in the Nigerian Ebola Response

Background: Outbreaks of infectious diseases such as Ebola have dramatic economic impacts on affected nations due to significant direct costs and indirect costs, as well as increased expenditure by the government to meet the health and security crisis. Despite its dense population, Nigeria was able to contain the outbreak swiftly and was declared Ebola free on 13th October 2014. Although Nigeria’s Ebola containment success was multifaceted, the private sector played a key role in Nigeria’s fight against Ebola. An epidemic of a disease like Ebola, not only consumes health resources but also detrimentally disrupts trade and travel to impact both public and private sector resulting in the ‘fearonomic’ effect of the contagion. In this thesis, I have defined ‘fearonomics’ or the ‘fearonomic effects’ of a disease as the intangible and intangible economic effects of both informed and misinformed aversion behavior exhibited by individuals, organizations, or countries during an outbreak. During an infectious disease outbreak, there is a significant potential for public-private sector collaborations that can help offset some of the government’s cost of controlling the epidemic.

Objective: The main objective of this study is to understand the ‘fearonomics’ of Ebola in Nigeria and to evaluate the role of the key private sector stakeholders in Nigeria’s Ebola response.

Methods: This retrospective qualitative study was conducted in Nigeria and utilizes grounded theory to look across different economic sectors in Nigeria to understand the impact of Ebola on Nigeria’s private sector and how it dealt with the various challenges posed by the disease and its ‘fearonomic effects'.

Results: Due to swift containment of Ebola in Nigeria, the economic impact of the disease was limited especially in comparison to the other Ebola-infected countries such as Liberia, Sierra Leone, and Guinea. However, the 2014 Ebola outbreak had more than a just direct impact on the country’s economy and despite the swift containment, no economic sector was immune to the disease’s fearonomic impact. The potential scale of the fearonomic impact of a disease like Ebola was one of the key motivators for the private sector engagement in the Ebola response.

The private sector in Nigeria played an essential role in facilitating the country’s response to Ebola. The private sector not only provided in-cash donations but significant in-kind support to both the Federal and State governments during the outbreak. Swift establishment of an Ebola Emergency Operation Centre (EEOC) was essential to the country’s response and was greatly facilitated by the private sector, showcasing the crucial role of private sector in the initial phase of an outbreak. The private sector contributed to Nigeria’s fight against Ebola not only by donating material assets but by continuing operations and partaking in knowledge sharing and advocacy. Some sector such as the private health sector, telecom sector, financial sector, oil and gas sector played a unique role in orchestrating the Nigerian Ebola response and were among the first movers during the outbreak.

This paper utilizes the lessons from Nigeria’s containment of Ebola to highlight the potential of public-private partnerships in preparedness, response, and recovery during an outbreak.

Hydrological Response of East China to the Variation of East Asian Summer Monsoon

Copyright © 2016 Fuxing Li et al.The sensitivity of hydrologic variables in East China, that is, runoff, precipitation, evapotranspiration, and soil moisture to the fluctuation of East Asian summer monsoon (EASM), is evaluated by the Mann-Kendall correlation analysis on a spatial resolution of 1/4° in the period of 1952-2012. The results indicate remarkable spatial disparities in the correlation between the hydrologic variables and EASM. The regions in East China susceptible to hydrological change due to EASM fluctuation are identified. When the standardized anomaly of intensity index of EASM (EASMI) is above 1.00, the runoff of Haihe basin has increased by 49% on average, especially in the suburb of Beijing and Hebei province where the runoff has increased up to 105%. In contrast, the runoff in the basins of Haihe and Yellow River has decreased by about 27% and 17%, respectively, when the standardized anomaly of EASMI is below -1.00, which has brought severe drought to the areas since mid-1970s. The study can be beneficial for national or watershed agencies developing adaptive water management strategies in the face of global climate change.