Modulating sensitivity to drug-induced apoptosis: the future for chemotherapy?

Drug resistance is a fundamental problem in the treatment of most common human cancers. Our understanding of the cellular mechanisms underlying death and survival has allowed the development of rational approaches to overcoming drug resistance. The mitogen activated protein kinase family of protein serine/threonine kinases has been implicated in this complex web of signalling, with some members acting to enhance death and other members to prevent it. A recent publication by MacKeigan et al is the first to demonstrate an enhancement of drug-induced cell death by simultaneous blockade of MEK-mediated survival signalling, and offers the potential for targeted adjuvant therapy as a means of overcoming drug resistance

The Numbers Behind Mushroom Biodiversity

Fungi are among the most diverse groups of organisms on Earth. with a global diversity estimated at 0.8 million to 5.1 million species. They play fundamental ecological roles as decomposers, mutualists, and pathogens, growing in almost all habitats and being important as sources of food and health benefits, income, and to maintain forest health. Global assessment of wild edible fungi indicate the existence of 2327 useful wild species; 2166 edible and 1069 used as food; 470 medicinal species. Several million tonnes are collected, consumed, and sold each year in over 80 countries. The major mushroom-producing countries in 2012 were China, Italy, USA, and The Netherlands, with 80% of the world production, 64% of which came from China. The European Union produces 24% of the world production. Italy is the largest European producer, Poland is the largest exporter, UK the largest importer.Fungi are difficult to preserve and fossilize and due to the poor preservation of most fungal structures, it has been difficult to interpret the fossil record of fungi. Hyphae, the vegetative bodies of fungi, bear few distinctive morphological characteristicss, and organisms as diverse as cyanobacteria, eukaryotic algal groups, and oomycetes can easily be mistaken for them (Taylor & Taylor 1993). Fossils provide minimum ages for divergences and genetic lineages can be much older than even the oldest fossil representative found. According to Berbee and Taylor (2010), molecular clocks (conversion of molecular changes into geological time) calibrated by fossils are the only available tools to estimate timing of evolutionary events in fossil‐poor groups, such as fungi. The arbuscular mycorrhizal symbiotic fungi from the division Glomeromycota, generally accepted as the phylogenetic sister clade to the Ascomycota and Basidiomycota, have left the most ancient fossils in the Rhynie Chert of Aberdeenshire in the north of Scotland (400 million years old). The Glomeromycota and several other fungi have been found associated with the preserved tissues of early vascular plants (Taylor et al. 2004a). Fossil spores from these shallow marine sediments from the Ordovician that closely resemble Glomeromycota spores and finely branched hyphae arbuscules within plant cells were clearly preserved in cells of stems of a 400 Ma primitive land plant, Aglaophyton, from Rhynie chert 455–460 Ma in age (Redecker et al. 2000; Remy et al. 1994) and from roots from the Triassic (250–199 Ma) (Berbee & Taylor 2010; Stubblefield et al. 1987).info:eu-repo/semantics/publishedVersio

The Youngest Victims: Children and Youth Affected by War

In 1989, the United Nation Convention on the Rights of the Child declared, “[state parties] shall take all feasible measures to ensure protection and care of children who are affected by an armed conflict.” In addition to attempting to secure the welfare of children in armed conflict, the Convention went on to ban the recruitment and deployment of children during armed conflict. Despite the vast majority of sovereign nations signing and ratifying this agreement, this treaty, unfortunately, has not prevented children and youth from witnessing, becoming victims of, or participating in political, ethnic, religious, and cultural violence across the past three decades. This chapter offers an “ecological perspective” on the psychosocial consequences of exposure to the trauma of war-related violence and social disruption

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Engaged parenting, gender, and children's time use in transnational families : an assessment spanning three global regions

Funding support for this study is from Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2015‐T2‐1‐008); Hong Kong Research Grants Council through its General Research Fund (Project 17606815); Wellcome Trust UK (GR079946/B/06/Z and GR079946/Z/06/Z).Global circuits of migration regularly separate parents from children. How families navigate this separation has changed markedly. The sharp decline in the cost of international communication makes possible new forms of transnational parenting. In many contexts, migrants are now actively engaged parents, involved in decisions, knowledgeable of children's schooling, employment, and activities, and in some cases, even conversant face‐to‐face with children via videoconferencing. These practices, however, are not universal. We use data from surveys in 3 countries to document the frequency and variability of intensive, engaged transnational parenting in the diverse global regions of Asia, Africa, and the Americas. We then ask whether the organisation of children's lives—specifically, time allocated to school homework, leisure, and household chores—varies by the degree to which migrant parents stay connected to sending homes. The gender of the migrant parent, stay‐behind caregiver, and the gender of the child emerge as explanatory factors for engaged parenting and children's time use. However, and unexpectedly, in the Philippines, migrant mothers are less likely to practice engaged parenting. In sending households, girls in two of the three countries spend more time doing household chores than boys, but parental migration does not mitigate this difference. Although we find some evidence of more traditional gender practices, we also find exceptions that suggest potentially fruitful avenues for future research.Publisher PDFPeer reviewe

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality