Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons

Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2. Progenies from both viruses were produced at equal quantities in iPSCs, neuroprogenitors and cortical neurons. HSV-1 and HSV-2 decreased viability of neuroprogenitors by 36.0% and 57.6% (p < 0.0001), respectively, 48 h post-infection, while cortical neurons were resilient to infection by both viruses. However, in these functional neurons, both HSV-1 and HSV-2 decreased gene expression of two markers of synaptic activity, CAMK2B and ARC, and affected synaptic activity negatively in multielectrode array experiments. However, unaltered secretion levels of the neurodegeneration markers tau and NfL suggested intact axonal integrity. Viral replication of both viruses was found after six days, coinciding with 6-fold and 22-fold increase in gene expression of cellular RNA polymerase II by HSV-1 and HSV-2, respectively. Our results suggest a resilience of human cortical neurons relative to the replication of HSV-1 and HSV-2

Nudging Cooperation in a Crowd Experiment

We examine the hypothesis that driven by a competition heuristic, people don't even reflect or consider whether a cooperation strategy may be better. As a paradigmatic example of this behavior we propose the zero-sum game fallacy, according to which people believe that resources are fixed even when they are not. We demonstrate that people only cooperate if the competitive heuristic is explicitly overridden in an experiment in which participants play two rounds of a game in which competition is suboptimal. The observed spontaneous behavior for most players was to compete. Then participants were explicitly reminded that the competing strategy may not be optimal. This minor intervention boosted cooperation, implying that competition does not result from lack of trust or willingness to cooperate but instead from the inability to inhibit the competition bias. This activity was performed in a controlled laboratory setting and also as a crowd experiment. Understanding the psychological underpinnings of these behaviors may help us improve cooperation and thus may have vast practical consequences to our society.Fil: Niella, Tamara. Universidad Torcuato di Tella; ArgentinaFil: Stier, Nicolas. Universidad Torcuato di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sigman, Mariano. Universidad Torcuato di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Engineering tyrosine residues into hemoglobin enhances heme reduction, decreases oxidative stress and increases vascular retention of a hemoglobin based blood substitute

Hemoglobin (Hb)-based oxygen carriers (HBOC) are modified extracellular proteins, designed to replace or augment the oxygen-carrying capacity of erythrocytes. However, clinical results have generally been disappointing due to adverse side effects, in part linked to the intrinsic oxidative toxicity of Hb. Previously a redox-active tyrosine residue was engineered into the Hb β subunit (βF41Y) to facilitate electron transfer between endogenous antioxidants such as ascorbate and the oxidative ferryl heme species, converting the highly oxidizing ferryl species into the less reactive ferric (met) form. We inserted different single tyrosine mutations into the α and β subunits of Hb to determine if this effect of βF41Y was unique. Every mutation that was inserted within electron transfer range of the protein surface and the heme increased the rate of ferryl reduction. However, surprisingly, three of the mutations (βT84Y, αL91Y and βF85Y) also increased the rate of ascorbate reduction of ferric(met) Hb to ferrous(oxy) Hb. The rate enhancement was most evident at ascorbate concentrations equivalent to that found in plasma (< 100 μM), suggesting that it might be of benefit in decreasing oxidative stress in vivo. The most promising mutant (βT84Y) was stable with no increase in autoxidation or heme loss. A decrease in membrane damage following Hb addition to HEK cells correlated with the ability of βT84Y to maintain the protein in its oxygenated form. When PEGylated and injected into mice, βT84Y was shown to have an increased vascular half time compared to wild type PEGylated Hb. βT84Y represents a new class of mutations with the ability to enhance reduction of both ferryl and ferric Hb, and thus has potential to decrease adverse side effects as one component of a final HBOC product

Sense of coherence and attrition during four-year follow-up in cohorts of permanent and non-permanent Finnish employees

<p>Abstract</p> <p>Background</p> <p>We studied whether health resources, measured as sense of coherence (SOC), are associated with participation in a follow-up survey among permanent and non-permanent employees who responded at baseline.</p> <p>Methods</p> <p>Of a cohort of 5,981 permanent employees, those who after four years were still in the service of the same employer were asked to participate in a follow-up survey. Another cohort consisted of 2,194 fixed-term and 682 subsidised employees; among these the follow-up survey was posted to those whose addresses were found in the population register. Non-participation was divided into loss to follow-up (i.e., failure to locate the individual, death and, among permanent employees, turnover or exit from labour market) and non-response to the follow-up survey. Logistic regression analyses were used to examine whether the respondents differed from the non-respondents with respect to SOC and other characteristics at baseline.</p> <p>Results</p> <p>Among permanent employees the follow-up survey yielded 3,998 respondents, 1,051 were lost, and 932 did not reply. Among non-permanent employees the follow-up survey yielded 1,563 respondents on initially fixed-term and 467 on subsidised contracts, the corresponding figures for those lost were 145 and 38, and for the non-respondents 486 and 177. Low SOC was associated with lower response rate among fixed-term but not among permanent or subsidised employees. No association was found between SOC and loss to follow-up.</p> <p>Conclusion</p> <p>SOC is a potential source of non-random sample attrition and should be taken into account for when estimating bias due to non-participation in occupational cohorts that include fixed-term employees.</p

A chronology of global air quality

Air pollution has been recognized as a threat to human health since the time of Hippocrates, ca 400 BC. Successive written accounts of air pollution occur in different countries through the following two millennia until measurements, from the eighteenth century onwards, show the growing scale of poor air quality in urban centres and close to industry, and the chemical characteristics of the gases and particulate matter. The industrial revolution accelerated both the magnitude of emissions of the primary pollutants and the geographical spread of contributing countries as highly polluted cities became the defining issue, culminating with the great smog of London in 1952. Europe and North America dominated emissions and suffered the majority of adverse effects until the latter decades of the twentieth century, by which time the transboundary issues of acid rain, forest decline and ground-level ozone became the main environmental and political air quality issues. As controls on emissions of sulfur and nitrogen oxides (SO2 and NOx) began to take effect in Europe and North America, emissions in East and South Asia grew strongly and dominated global emissions by the early years of the twenty-first century. The effects of air quality on human health had also returned to the top of the priorities by 2000 as new epidemiological evidence emerged. By this time, extensive networks of surface measurements and satellite remote sensing provided global measurements of both primary and secondary pollutants. Global emissions of SO2 and NOx peaked, respectively, in ca 1990 and 2018 and have since declined to 2020 as a result of widespread emission controls. By contrast, with a lack of actions to abate ammonia, global emissions have continued to grow

Dutch women with a low birth weight have an increased risk of myocardial infarction later in life: a case control study

BACKGROUND: To investigate whether low birth weight increases the risk of myocardial infarction later in life in women. METHODS: Nationwide population-based case-control study. Patients and controls: 152 patients with a first myocardial infarction before the age of 50 years in the Netherlands. 568 control women who had not had a myocardial infarction stratified for age, calendar year of the index event, and area of residence. RESULTS: Birth weight in the patient group was significantly lower than in control women (3214 vs. 3370 gram, mean difference -156.3 gram (95%CI -9.5 to -303.1). The odds ratio for myocardial infarction, associated with a birth weight lower than 3000 gram (20(th )percentile in controls) compared to higher than 3000 gram was 1.7 (95%CI 1.1–2.7), while the odds ratio for myocardial infarction for children with a low birth weight (< 2000 g) compared to a birth weight ≥ 2000 g was 2.4 (95%CI 1.0 – 5.8). Both figures did not change after adjustment for putative confounders (age, education level, body mass index, waist-hip ratio, hypertension, diabetes, hypercholesterolemia, smoking, and family history of cardiovascular disease). CONCLUSIONS: Low birth weight is associated with an increased risk of myocardial infarction before age of 50 in Dutch women

A resource-based view and dynamic capabilities approach in the context of a region’s international attractiveness: The recent case of Western Australia

This exploratory study proposes a framework based on the resource view theory and the dynamic capabilities approach to further the understanding of a region’s attractiveness, particularly from an international perspective. The case of Western Australia is examined through in-depth, face-to-face interviews with nine country consuls experienced in international trade. The findings revealed significant ways in which Western Australia could enhance its future commercial appeal. The findings revealed the value of synergies between this state and other countries, particularly exchanging expertise, transferring knowledge, or exporting know-how, education, both university and industry-focused, research and development and expertise. These forms of regional attractiveness emphasise the strategic role of industry resources and dynamic capabilities, thus, underscoring the usefulness and applicability of the proposed framework. While the state’s mineral exports will continue to drive its economy, harnessing its potential in other areas is crucial to adapt to changing business environments and to build sustained competitive advantage. © 2018, The Author(s) 2018

A Novel Biochemical Route for Fuels and Chemicals Production from Cellulosic Biomass

The conventional biochemical platform featuring enzymatic hydrolysis involves five key steps: pretreatment, cellulase production, enzymatic hydrolysis, fermentation, and product recovery. Sugars are produced as reactive intermediates for subsequent fermentation to fuels and chemicals. Herein, an alternative biochemical route is proposed. Pretreatment, enzymatic hydrolysis and cellulase production is consolidated into one single step, referred to as consolidated aerobic processing, and sugar aldonates are produced as the reactive intermediates for biofuels production by fermentation. In this study, we demonstrate the viability of consolidation of the enzymatic hydrolysis and cellulase production steps in the new route using Neurospora crassa as the model microorganism and the conversion of cellulose to ethanol as the model system. We intended to prove the two hypotheses: 1) cellulose can be directed to produce cellobionate by reducing β-glucosidase production and by enhancing cellobiose dehydrogenase production; and 2) both of the two hydrolysis products of cellobionate—glucose and gluconate—can be used as carbon sources for ethanol and other chemical production. Our results showed that knocking out multiple copies of β-glucosidase genes led to cellobionate production from cellulose, without jeopardizing the cellulose hydrolysis rate. Simulating cellobiose dehydrogenase over-expression by addition of exogenous cellobiose dehydrogenase led to more cellobionate production. Both of the two hydrolysis products of cellobionate: glucose and gluconate can be used by Escherichia coli KO 11 for efficient ethanol production. They were utilized simultaneously in glucose and gluconate co-fermentation. Gluconate was used even faster than glucose. The results support the viability of the two hypotheses that lay the foundation for the proposed new route