El Niño, tropical Atlantic warmth, and Atlantic hurricanes over the past 1500 years

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 460 (2009): 880-883, doi:10.1038/nature08219.Atlantic Tropical Cyclone (TC) activity, as measured by annual storm counts, reached anomalous levels over the past decade. The short nature of the historical record and potential issues with its reliability in earlier decades, however, has prompted an ongoing debate regarding the reality and significance of the recent rise. Here, we place recent activity in a longer-term context, by comparing two independent estimates of TC activity over the past 1500 years. The first estimate is based on a composite of regional sedimentary evidence of landfalling hurricanes, while the second estimate employs a previously published statistical model of Atlantic TC activity driven by proxy-reconstructions of past climate changes. Both approaches yield consistent evidence of a peak in Atlantic TC activity during Medieval times (around AD 1000) followed by a subsequent lull in activity. The Medieval peak, which rivals or even exceeds (within uncertainties) recent levels of activity, results in the statistical model from a ‘perfect storm’ of La Niña-like climate conditions and relative tropical Atlantic warmth.M.E.M. and Z.Z. acknowledge support from the ATM programme of the National Science Foundation (grant ATM-0542356). J.P.D. acknowledges support from the EAR and OCE programmes of the National Science Foundation (grants EAR-0519118 and OCE-0402746), the Risk Prediction Initiative at the Bermuda Institute for Ocean Sciences, and the Inter-American Institute for Global Change Research

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

Cerebellar-dependent delay eyeblink conditioning in adolescents with Specific Language Impairment

Cerebellar impairments have been hypothesized as part of the pathogenesis of Specific Language Impairment (SLI), although direct evidence of cerebellar involvement is sparse. Eyeblink Conditioning (EBC) is a learning task with well documented cerebellar pathways. This is the first study of EBC in affected adolescents and controls. 16 adolescent controls, 15 adolescents with SLI, and 12 adult controls participated in a delay EBC task. Affected children had low general language performance, grammatical deficits but no speech impairments. The affected group did not differ from the control adolescent or control adult group, showing intact cerebellar functioning on the EBC task. This study did not support cerebellar impairment at the level of basic learning pathways as part of the pathogenesis of SLI. Outcomes do not rule out cerebellar influences on speech impairment, or possible other forms of cerebellar functioning as contributing to SLI

Insufficient OPC migration into demyelinated lesions is a cause of poor remyelination in MS and mouse models

Failure of remyelination of multiple sclerosis (MS) lesions contributes to neurodegeneration that correlates with chronic disability in patients. Currently, there are no available treatments to reduce neurodegeneration, but one therapeutic approach to fill this unmet need is to promote remyelination. As many demyelinated MS lesions contain plentiful oligodendrocyte precursor cells (OPCs), but no mature myelinating oligodendrocytes, research has previously concentrated on promoting OPC maturation. However, some MS lesions contain few OPCs, and therefore, remyelination failure may also be secondary to OPC recruitment failure. Here, in a series of MS samples, we determined how many lesions contained few OPCs, and correlated this to pathological subtype and expression of the chemotactic molecules Semaphorin (Sema) 3A and 3F. 37 % of MS lesions contained low numbers of OPCs, and these were mostly chronic active lesions, in which cells expressed Sema3A (chemorepellent). To test the hypothesis that differential Sema3 expression in demyelinated lesions alters OPC recruitment and the efficiency of subsequent remyelination, we used a focal myelinotoxic mouse model of demyelination. Adding recombinant (r)Sema3A (chemorepellent) to demyelinated lesions reduced OPC recruitment and remyelination, whereas the addition of rSema3F (chemoattractant), or use of transgenic mice with reduced Sema3A expression increased OPC recruitment and remyelination. We conclude that some MS lesions fail to remyelinate secondary to reduced OPC recruitment, and that chemotactic molecules are involved in the mechanism, providing a new group of drug targets to improve remyelination, with a specific target in the Sema3A receptor neuropilin-1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-013-1112-y) contains supplementary material, which is available to authorized users

Measures of low food variety and poor dietary quality in a cross-sectional study of London school children.

BACKGROUND/OBJECTIVES: The use of simple screening tools to measure nutritional adequacy in a public health context in developed countries are currently lacking. We explore the relationship between food variety and nutrient intake of London school children using a simple tool with potential use for screening for inadequate diets. SUBJECTS/METHODS: A cross-sectional survey was carried out in 2010. The survey included 2579 children aged 7-10 years in 52 primary schools in East London in the United Kingdom. The analysis included 2392 children (93% of the original sample). Food variety was assessed as the total number of listed foods recorded over 24 h using the validated Child and Diet Assessment Tool (CADET) comprising 115 listed foods divided into 16 food categories. Dietary quality was determined by the proportion of children meeting recommended intakes of individual micronutrients, namely, calcium, iron, zinc, folate, vitamin A and vitamin C. RESULTS: The mean number of CADET-listed foods consumed daily by children was 17.1 (95% CI: 16.8, 17.5). Children who consumed fewer than 11 foods on the collection day had particularly low nutrient intakes. Children consuming three different vegetables and two different fruits on average consumed 19-20 listed foods. It was estimated between 4 and 20% of children did not meet the recommended levels for individual micronutrients during the period of data collection. CONCLUSIONS: A simple method using food counts to assess daily food variety may help public health nutritionists identify groups of children at risk of inadequate diets

Divergence across mitochondrial genomes of sympatric members of the Schistosoma indicum group and clues into the evolution of Schistosoma spindale

Schistosoma spindale and Schistosoma indicum are ruminant-infecting trematodes of the Schistosoma indicum group that are widespread across Southeast Asia. Though neglected, these parasites can cause major pathology and mortality to livestock leading to significant welfare and socio-economic issues, predominantly amongst poor subsistence farmers and their families. Here we used mitogenomic analysis to determine the relationships between these two sympatric species of schistosome and to characterise S. spindale diversity in order to identify possible cryptic speciation. The mitochondrial genomes of S. spindale and S. indicum were assembled and genetic analyses revealed high levels of diversity within the S. indicum group. Evidence of functional changes in mitochondrial genes indicated adaptation to environmental change associated with speciation events in S. spindale around 2.5 million years ago. We discuss our results in terms of their theoretical and applied implications

Adaptation of a Smoking Cessation and Prevention Website for Urban American Indian/Alaska Native Youth

Tobacco use among American Indian youth is a disproportionately significant problem. We adapted and modified an existing web-based and youth-focused tobacco control program to make it appropriate for young urban American Indian/Alaska Natives (AI/ANs). The results of the focus group indicate that AI/AN youth were very receptive to the use of a web-based Zine-style intervention tool. They wanted the look and feel of the website to be more oriented toward their cultural images. Future research should examine if successful programs for reducing non-ceremonial tobacco use among urban AI/AN youth can keep young irregular smokers from becoming adult smokers

Where Do We Go from Here? Prevalence of Trachoma Three Years after Stopping Mass Distribution of Antibiotics in the Regions of Kayes and Koulikoro, Mali

Trachoma, a blinding bacterial disease, is targeted for elimination by 2020. To achieve the elimination target, the World Health Organization (WHO) recommends member states implement the SAFE strategy; surgery, mass administration of antibiotics, promotion of hygiene and facial cleanliness and water and sanitation as environmental improvements. We present results from evaluation surveys conducted in 2006 and 2009 from the regions of Kayes and Koulikoro, Mali. Prevalence of active trachoma in 2006 was below baseline intervention thresholds in all surveyed districts and the national program stopped antibiotic distribution. The prevalence of trachoma in 2009 remained well below levels in 1998. However, in 8 of 13 districts compared, the prevalence of active trachoma was higher in 2009 than 2006. Three years of antibiotic intervention did not equate in all districts to a sustained reduction of active trachoma. No surveillance activities were implemented after stopping interventions. Surgical interventions may have reduced the burden of blinding trachoma but there is an ongoing need for surgeries specifically targeting affected women. Four districts meet the WHO criteria for resuming district-wide mass antibiotic distribution. A community-by-community approach to elimination may be needed in other districts. The promotion of facial cleanliness and good hygiene behavior should be reintroduced

Multifunctional Role of Bcl-2 in Malignant Transformation and Tumorigenesis of Cr(VI)-Transformed Lung Cells

B-cell lymphoma-2 (Bcl-2) is an antiapoptotic protein known to be important in the regulation of apoptosis in various cell types. However, its role in malignant transformation and tumorigenesis of human lung cells is not well understood. We previously reported that chronic exposure of human lung epithelial cells to the carcinogenic hexavalent chromium Cr(VI) caused malignant transformation and Bcl-2 upregulation; however, the role of Bcl-2 in the transformation is unclear. Using a gene silencing approach, we showed that Bcl-2 plays an important role in the malignant properties of Cr(VI)-transformed cells. Downregulation of Bcl-2 inhibited the invasive and proliferative properties of the cells as well as their colony forming and angiogenic activities, which are upregulated in the transformed cells as compared to control cells. Furthermore, animal studies showed the inhibitory effect of Bcl-2 knockdown on the tumorigenesis of Cr(VI)-transformed cells. The role of Bcl-2 in malignant transformation and tumorigenesis was confirmed by gene silencing experiments using human lung carcinoma NCI-H460 cells. These cells exhibited aggressive malignant phenotypes similar to those of Cr(VI)-transformed cells. Knockdown of Bcl-2 in the H460 cells inhibited malignant and tumorigenic properties of the cells, indicating the general role of Bcl-2 in human lung tumorigenesis. Ingenuity Pathways Analysis (IPA) revealed potential effectors of Bcl-2 in tumorigenesis regulation. Additionally, using IPA together with ectopic expression of p53, we show p53 as an upstream regulator of Bcl-2 in Cr(VI)-transformed cells. Together, our results indicate the novel and multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of human lung epithelial cells chronically exposed to Cr(VI)