Guidelines for Reporting and Archiving 210Pb Sediment Chronologies to Improve Fidelity and Extend Data Lifecycle

Radiometric dating methods are essential for developing geochronologies to study Late Quaternary environmental change and 210Pb dating is commonly used to produce age-depth models from recent (within 150 years) sediments and other geoarchives. The past two centuries are marked by rapid environmental socio-ecological changes frequently attributed to anthropogenic land-use activities, modified biogeochemical cycles, and climate change. Consequently, historical reconstructions over this recent time interval have high societal value because analyses of these datasets provide understanding of the consequences of environmental modifications, critical ecosystem thresholds, and to define desirable ranges of variation for management, restoration, and conservation. For this information to be used more broadly, for example to support land management decisions or to contribute data to regional analyses of ecosystem change, authors must report all of the useful age-depth model information. However, at present there are no guidelines for researchers on what information should be reported to ensure 210Pb data are fully disclosed, reproducible, and reusable; leading to a plethora of reporting styles, including inadequate reporting that reduces potential reusability and shortening the data lifecycle. For example, 64% of the publications in a literature review of 210Pb dated geoarchives did not include any presentation of age uncertainty estimates in modeled calendar ages used in age-depth models. Insufficient reporting of methods and results used in 210Pb dating geoarchives severely hampers reproducibility and data reusability, especially in analyses that make use of databased palaeoenvironmental data. Reproducibility of data is fundamental to further analyses of the number of palaeoenvironmental data and the spatial coverage of published geoarchives sites. We suggest, and justify, a set of minimum reporting guidelines for metadata and data reporting for 210Pb dates, including an IEDA (Interdisciplinary Earth Data Alliance), LiPD (Linked Paleo Data) and generic format data presentation templates, to contribute to improvements in data archiving standards and to facilitate the data requirements of researchers analyzing datasets of several palaeoenvironmental study sites. We analyse practices of methods, results and first order interpretation of 210Pb data and make recommendations to authors on effective data reporting and archiving to maximize the value of datasets. We provide empirical evidence from publications and practitioners to support our suggested reporting guidelines. These guidelines increase the scientific value of 210Pb by expanding its relevance in the data lifecycle. Improving quality and fidelity of environmental datasets broadens interdisciplinary use, lengthens the potential lifecycle of data products, and achieves requirements applicable for evidenced-based policy support

Abrupt high-latitude climate events and decoupled seasonal trends during the Eemian

The Eemian (the Last Interglacial; ca. 129-116 thousand years ago) presents a testbed for assessing environmental responses and climate feedbacks under warmer-than-present boundary conditions. However, climate syntheses for the Eemian remain hampered by lack of data from the high-latitude land areas, masking the climate response and feedbacks in the Arctic. Here we present a high-resolution (sub-centennial) record of Eemian palaeoclimate from northern Finland, with multi-model reconstructions for July and January air temperature. In contrast with the mid-latitudes of Europe, our data show decoupled seasonal trends with falling July and rising January temperatures over the Eemian, due to orbital and oceanic forcings. This leads to an oceanic Late-Eemian climate, consistent with an earlier hypothesis of glacial inception in Europe. The interglacial is further intersected by two strong cooling and drying events. These abrupt events parallel shifts in marine proxy data, linked to disturbances in the North Atlantic oceanic circulation regime.Peer reviewe

Macrosystems ecology: Understanding ecological patterns and processes at continental scales

Macrosystems ecology is the study of diverse ecological phenomena at the scale of regions to continents and their interactions with phenomena at other scales. This emerging subdiscipline addresses ecological questions and environmental problems at these broad scales. Here, we describe this new field, show how it relates to modern ecological study, and highlight opportunities that stem from taking a macrosystems perspective. We present a hierarchical framework for investigating macrosystems at any level of ecological organization and in relation to broader and finer scales. Building on well-established theory and concepts from other subdisciplines of ecology, we identify feedbacks, linkages among distant regions, and interactions that cross scales of space and time as the most likely sources of unexpected and novel behaviors in macrosystems. We present three examples that highlight the importance of this multiscaled systems perspective for understanding the ecology of regions to continents

Statistically-Estimated Tree Composition for the Northeastern United States at Euro-American Settlement

We present a gridded 8 km-resolution data product of the estimated composition of tree taxa at the time of Euro-American settlement of the northeastern United States and the statistical methodology used to produce the product from trees recorded by land surveyors. Composition is defined as the proportion of stems larger than approximately 20 cm diameter at breast height for 22 tree taxa, generally at the genus level. The data come from settlement-era public survey records that are transcribed and then aggregated spatially, giving count data. The domain is divided into two regions, eastern (Maine to Ohio) and midwestern (Indiana to Minnesota). Public Land Survey point data in the midwestern region (ca. 0.8-km resolution) are aggregated to a regular 8 km grid, while data in the eastern region, from Town Proprietor Surveys, are aggregated at the township level in irregularly-shaped local administrative units. The product is based on a Bayesian statistical model fit to the count data that estimates composition on the 8 km grid across the entire domain. The statistical model is designed to handle data from both the regular grid and the irregularly-shaped townships and allows us to estimate composition at locations with no data and to smooth over noise caused by limited counts in locations with data. Critically, the model also allows us to quantify uncertainty in our composition estimates, making the product suitable for applications employing data assimilation. We expect this data product to be useful for understanding the state of vegetation in the northeastern United States prior to large-scale Euro-American settlement. In addition to specific regional questions, the data product can also serve as a baseline against which to investigate how forests and ecosystems change after intensive settlement. The data product is being made available at the NIS data portal as version 1.0

Climatic history of the northeastern United States during the past 3000 years

Many ecosystem processes that influence Earth system feedbacks – vegetation growth, water and nutrient cycling, disturbance regimes – are strongly influenced by multidecadal- to millennial-scale climate variations that cannot be directly observed. Paleoclimate records provide information about these variations, forming the basis of our understanding and modeling of them. Fossil pollen records are abundant in the NE US, but cannot simultaneously provide information about paleoclimate and past vegetation in a modeling context because this leads to circular logic. If pollen data are used to constrain past vegetation changes, then the remaining paleoclimate archives in the northeastern US (NE US) are quite limited. Nonetheless, a growing number of diverse reconstructions have been developed but have not yet been examined together. Here we conduct a systematic review, assessment, and comparison of paleotemperature and paleohydrological proxies from the NE US for the last 3000 years. Regional temperature reconstructions (primarily summer) show a long-term cooling trend (1000 BCE–1700 CE) consistent with hemispheric-scale reconstructions, while hydroclimate data show gradually wetter conditions through the present day. Multiple proxies suggest that a prolonged, widespread drought occurred between 550 and 750 CE. Dry conditions are also evident during the Medieval Climate Anomaly, which was warmer and drier than the Little Ice Age and drier than today. There is some evidence for an acceleration of the longer-term wetting trend in the NE US during the past century; coupled with an abrupt shift from decreasing to increasing temperatures in the past century, these changes could have wide-ranging implications for species distributions, ecosystem dynamics, and extreme weather events. More work is needed to gather paleoclimate data in the NE US to make inter-proxy comparisons and to improve estimates of uncertainty in reconstructions

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Validation Study of Existing Gene Expression Signatures for Anti-TNF Treatment in Patients with Rheumatoid Arthritis

So far, there are no means of identifying rheumatoid arthritis (RA) patients who will fail to respond to tumour necrosis factor blocking agents (anti-TNF), prior to treatment. We set out to validate eight previously reported gene expression signatures predicting therapy outcome. Genome-wide expression profiling using Affymetrix GeneChip Exon 1.0 ST arrays was performed on RNA isolated from whole blood of 42 RA patients starting treatment with infliximab or adalimumab. Clinical response according to EULAR criteria was determined at week 14 of therapy. Genes that have been reported to be associated with anti-TNF treatment were extracted from our dataset. K-means partition clustering was performed to assess the predictive value of the gene-sets. We performed a hypothesis-driven analysis of the dataset using eight existing gene sets predictive of anti-TNF treatment outcome. The set that performed best reached a sensitivity of 71% and a specificity of 61%, for classifying the patients in the current study. We successfully validated one of eight previously reported predictive expression profile. This replicated expression signature is a good starting point for developing a prediction model for anti-TNF treatment outcome that can be used in a daily clinical setting. Our results confirm that gene expression profiling prior to treatment is a useful tool to predict anti-TNF (non) response

Modifier Effects between Regulatory and Protein-Coding Variation

Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants

The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study

While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (FA) to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes). The unique study design (Matched Co-Twin Analysis—MCTA) permits immediate replication of eQTLs using co-twins (93%–98%) and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%–20%) have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field