The intertropical convergence zone modulates intense hurricane strikes on the western North Atlantic margin

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 21728, doi:10.1038/srep21728Most Atlantic hurricanes form in the Main Development Region between 9°N to 20°N along the northern edge of the Intertropical Convergence Zone (ITCZ). Previous research has suggested that meridional shifts in the ITCZ position on geologic timescales can modulate hurricane activity, but continuous and long-term storm records are needed from multiple sites to assess this hypothesis. Here we present a 3000 year record of intense hurricane strikes in the northern Bahamas (Abaco Island) based on overwash deposits in a coastal sinkhole, which indicates that the ITCZ has likely helped modulate intense hurricane strikes on the western North Atlantic margin on millennial to centennial-scales. The new reconstruction closely matches a previous reconstruction from Puerto Rico, and documents a period of elevated intense hurricane activity on the western North Atlantic margin from 2500 to 1000 years ago when paleo precipitation proxies suggest that the ITCZ occupied a more northern position. Considering that anthropogenic warming is predicted to be focused in the northern hemisphere in the coming century, these results provide a prehistoric analog that an attendant northern ITCZ shift in the future may again return the western North Atlantic margin to an active hurricane interval.This research was supported by NSF Awards: OCE-1519578, OCE-1356708, BCS-1118340

Transcriptomic comparison of the retina in two mouse models of diabetes

Mouse models of type I diabetes offer the potential to combine genetic approaches with other pharmacological or physiological manipulations to investigate the pathophysiology and treatment of diabetic retinopathy. Type I diabetes is induced in mice through chemical toxins or can arise spontaneously from genetic mutations. Both models are associated with retinal vascular and neuronal changes. Retinal transcriptomic responses in C57BL/6J mice treated with streptozotocin and Ins2Akita/+ were compared after 3 months of hyperglycemia. Specific gene expression changes suggest a neurovascular inflammatory response in diabetic retinopathy. Genes common to the two models may represent the response of the retina to hyperglycemia, while changes unique to each model may represent time-dependent disease progression differences in the various models. Further investigation of the commonalities and differences between mouse models of type I diabetes may define cause and effect events in early diabetic retinopathy disease progression

Whole genome assessment of the retinal response to diabetes reveals a progressive neurovascular inflammatory response

<p>Abstract</p> <p>Background</p> <p>Despite advances in the understanding of diabetic retinopathy, the nature and time course of molecular changes in the retina with diabetes are incompletely described. This study characterized the functional and molecular phenotype of the retina with increasing durations of diabetes.</p> <p>Results</p> <p>Using the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Increased levels of vascular permeability and caspase-3 activity were observed at 3 months of diabetes, but not 1 month. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes. Quantitative PCR validation of selected genes related to inflammation, microvasculature and neuronal function confirmed gene expression changes in multiple independent sets of animals.</p> <p>Conclusion</p> <p>These changes in permeability, apoptosis, and gene expression provide further evidence of progressive retinal malfunction with increasing duration of diabetes. The specific gene expression changes confirmed in multiple sets of animals indicate that pro-inflammatory, anti-vascular barrier, and neurodegenerative changes occur in tandem with functional increases in apoptosis and vascular permeability. These responses are shared with the clinically documented inflammatory response in diabetic retinopathy suggesting that this model may be used to test anti-inflammatory therapeutics.</p

Visualizing early splenic memory CD8+ T cells reactivation against intracellular bacteria in the mouse

International audienceMemory CD8(+) T cells represent an important effector arm of the immune response in maintaining long-lived protective immunity against viruses and some intracellular bacteria such as Listeria monocytogenes (L.m). Memory CD8(+) T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens. It is largely accepted that these functions are sufficient to explain how memory CD8(+) T cells can mediate rapid protection. However, it is important to point out that such improved functional features would be useless if memory cells were unable to rapidly find the pathogen loaded/infected cells within the infected organ. Growing evidences suggest that the anatomy of secondary lymphoid organs (SLOs) fosters the cellular interactions required to initiate naive adaptive immune responses. However, very little is known on how the SLOs structures regulate memory immune responses. Using Listeria monocytogenes (L.m) as a murine infection model and imaging techniques, we have investigated if and how the architecture of the spleen plays a role in the reactivation of memory CD8(+) T cells and the subsequent control of L.m growth. We observed that in the mouse, memory CD8(+) T cells start to control L.m burden 6 hours after the challenge infection. At this very early time point, L.m-specific and non-specific memory CD8(+) T cells localize in the splenic red pulp and form clusters around L.m infected cells while naïve CD8(+) T cells remain in the white pulp. Within these clusters that only last few hours, memory CD8(+) T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing. Altogether, we describe how memory CD8(+) T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+) T cells provide a local response by secreting effector molecules around infected cells

Large Tandem, Higher Order Repeats and Regularly Dispersed Repeat Units Contribute Substantially to Divergence Between Human and Chimpanzee Y Chromosomes

Comparison of human and chimpanzee genomes has received much attention, because of paramount role for understanding evolutionary step distinguishing us from our closest living relative. In order to contribute to insight into Y chromosome evolutionary history, we study and compare tandems, higher order repeats (HORs), and regularly dispersed repeats in human and chimpanzee Y chromosome contigs, using robust Global Repeat Map algorithm. We find a new type of long-range acceleration, human-accelerated HOR regions. In peripheral domains of 35mer human alphoid HORs, we find riddled features with ten additional repeat monomers. In chimpanzee, we identify 30mer alphoid HOR. We construct alphoid HOR schemes showing significant human-chimpanzee difference, revealing rapid evolution after human-chimpanzee separation. We identify and analyze over 20 large repeat units, most of them reported here for the first time as: chimpanzee and human ~1.6 kb 3mer secondary repeat unit (SRU) and ~23.5 kb tertiary repeat unit (~0.55 kb primary repeat unit, PRU); human 10848, 15775, 20309, 60910, and 72140 bp PRUs; human 3mer SRU (~2.4 kb PRU); 715mer and 1123mer SRUs (5mer PRU); chimpanzee 5096, 10762, 10853, 60523 bp PRUs; and chimpanzee 64624 bp SRU (10853 bp PRU). We show that substantial human-chimpanzee differences are concentrated in large repeat structures, at the level of as much as ~70% divergence, sizably exceeding previous numerical estimates for some selected noncoding sequences. Smeared over the whole sequenced assembly (25 Mb) this gives ~14% human--chimpanzee divergence. This is significantly higher estimate of divergence between human and chimpanzee than previous estimates.Comment: 22 pages, 7 figures, 12 tables. Published in Journal of Molecular Evolutio

The ACER pollen and charcoal database: A global resource to document vegetation and fire response to abrupt climate changes during the last glacial period

This is the final version of the article. Available from Copernicus Publications via the DOI in this record.Quaternary records provide an opportunity to examine the nature of the vegetation and fire responses to rapid past climate changes comparable in velocity and magnitude to those expected in the 21st-century. The best documented examples of rapid climate change in the past are the warming events associated with the Dansgaard-Oeschger (D-O) cycles during the last glacial period, which were sufficiently large to have had a potential feedback through changes in albedo and greenhouse gas emissions on climate. Previous reconstructions of vegetation and fire changes during the D-O cycles used independently constructed age models, making it difficult to compare the changes between different sites and regions. Here, we present the ACER (Abrupt Climate Changes and Environmental Responses) global database, which includes 93 pollen records from the last glacial period (73-15ka) with a temporal resolution better than 1000years, 32 of which also provide charcoal records. A harmonized and consistent chronology based on radiometric dating (14C, 234U/230Th, optically stimulated luminescence (OSL), 40Ar/39Ar-dated tephra layers) has been constructed for 86 of these records, although in some cases additional information was derived using common control points based on event stratigraphy. The ACER database compiles metadata including geospatial and dating information, pollen and charcoal counts, and pollen percentages of the characteristic biomes and is archived in Microsoft Access™ at https://doi.org/10.1594/PANGAEA.870867.The members of the ACER project wish to thank the QUEST-DESIRE (UK and France) bilateral project, the INQUA International Focus Group ACER and the INTIMATE-COST action for funding a suite of workshops to compile the ACER pollen and charcoal database and the workshop on ACER chronology that allow setting the basis for harmonizing the chronologies. Josué M. Polanco-Martinez was funded by a Basque Government postdoctoral fellowship (POS_2015_1_0006) and Sandy P. Harrison by the ERC Advanced Grant GC2.0: unlocking the past for a clearer future

Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome

<p>Abstract</p> <p>Background</p> <p>Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Approximately 95% of patients with Type 1 diabetes develop some degree of retinopathy within 25 years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify molecular changes in the rodent retina induced by diabetes that are not normalized by insulin replacement and restoration of euglycemia.</p> <p>Methods</p> <p>The retina transcriptome (22,523 genes and transcript variants) was examined after three months of streptozotocin-induced diabetes in male Sprague Dawley rats with and without insulin replacement for the later one and a half months of diabetes. Selected gene expression changes were confirmed by qPCR, and also examined in independent control and diabetic rats at a one month time-point.</p> <p>Results</p> <p>Transcriptomic alterations in response to diabetes (1376 probes) were clustered according to insulin responsiveness. More than half (57%) of diabetes-induced mRNA changes (789 probes) observed at three months were fully normalized to control levels with insulin therapy, while 37% of probes (514) were only partially normalized. A small set of genes (5%, 65 probes) was significantly dysregulated in the insulin-treated diabetic rats. qPCR confirmation of findings and examination of a one month time point allowed genes to be further categorized as prevented or rescued with insulin therapy. A subset of genes (Ccr5, Jak3, Litaf) was confirmed at the level of protein expression, with protein levels recapitulating changes in mRNA expression.</p> <p>Conclusions</p> <p>These results provide the first genome-wide examination of the effects of insulin therapy on retinal gene expression changes with diabetes. While insulin clearly normalizes the majority of genes dysregulated in response to diabetes, a number of genes related to inflammatory processes, microvascular integrity, and neuronal function are still altered in expression in euglycemic diabetic rats. Gene expression changes not rescued or prevented by insulin treatment may be critical to the pathogenesis of diabetic retinopathy, as it occurs in diabetic patients receiving insulin replacement, and are prototypical of metabolic memory.</p

Inspired or foolhardy: sensemaking, confidence and entrepreneurs' decision-making.

The purpose of this paper is to investigate the role of confidence in how both new and experienced entrepreneurs interpret and make sense of their business environment to inform decision-making. We illustrate our conceptual arguments with descriptive results from a large-scale (n = 6289) survey on entrepreneurs' perception of business performance and their decisions taken at a time of uncertainty in an economic downturn. Quantitative findings are stratified along experiential lines to explore heterogeneity in entrepreneurial decision-making and directly inform our conceptual arguments, while qualitative data from open questions are used to explain the role of confidence. Newer entrepreneurs are found to be more optimistic in the face of environmental risk, which impacts on their decision-making and innovative capabilities. However, the more experienced entrepreneurs warily maintain margin and restructure to adapt to environmental changes. Instead of looking directly at the confidence of individuals, we show how confidence impacts sensemaking, and ultimately, decision-making. These insights inform research on the behaviour of novice and experienced entrepreneurs in relation to innovative business activities. Specifically, blanket assumptions on the role of confidence may be misplaced as its impact changes with experience to alter how entrepreneurs make sense of their environment

The case for strategic international alliances to harness nutritional genomics for public and personal health

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countrie

Multi-Modal Proteomic Analysis of Retinal Protein Expression Alterations in a Rat Model of Diabetic Retinopathy

As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies.A multi-modal proteomic approach of antibody (Luminex)-, electrophoresis (DIGE)-, and LC-MS (iTRAQ)-based quantitation methods was used to maximize coverage of the retinal proteome. Transcriptomic profiling through microarray analysis was included to identify additional targets and assess potential regulation of protein expression changes at the mRNA level. The proteomic approaches proved complementary, with limited overlap in proteomic coverage. Alterations in pro-inflammatory, signaling and crystallin family proteins were confirmed by orthogonal methods in multiple independent animal cohorts. In an independent experiment, insulin replacement therapy normalized the expression of some proteins (Dbi, Anxa5) while other proteins (Cp, Cryba3, Lgals3, Stat3) were only partially normalized and Fgf2 and Crybb2 expression remained elevated.These results expand the understanding of the changes in retinal protein expression occurring with diabetes and their responsiveness to normalization of blood glucose through insulin therapy. These proteins, especially those not normalized by insulin therapy, may also be useful in preclinical drug development studies