BASiCS: Bayesian Analysis of Single-Cell Sequencing Data

Single-cell mRNA sequencing can uncover novel cell-to-cell heterogeneity in gene expression levels in seemingly homogeneous populations of cells. However, these experiments are prone to high levels of unexplained technical noise, creating new challenges for identifying genes that show genuine heterogeneous expression within the population of cells under study. BASiCS (Bayesian Analysis of Single-Cell Sequencing data) is an integrated Bayesian hierarchical model where: (i) cell-specific normalisation constants are estimated as part of the model parameters, (ii) technical variability is quantified based on spike-in genes that are artificially introduced to each analysed cell's lysate and (iii) the total variability of the expression counts is decomposed into technical and biological components. BASiCS also provides an intuitive detection criterion for highly (or lowly) variable genes within the population of cells under study. This is formalised by means of tail posterior probabilities associated to high (or low) biological cell-to-cell variance contributions, quantities that can be easily interpreted by users. We demonstrate our method using gene expression measurements from mouse Embryonic Stem Cells. Cross-validation and meaningful enrichment of gene ontology categories within genes classified as highly (or lowly) variable supports the efficacy of our approach

Nondaily Deposition Of Striae In The Bay Scallop Argopecten Irradians (Concentricus) In The Laboratory

Small (similar to 15 mm) and large (similar to 30 mm) calcein-marked bay scallops, Argopecten irradians, held for 2, 4, and 6 wk in the laboratory under natural illumination and conditions of high and low flow rates deposited significantly more striae on the surface of the left (dark) shell valve compared with the right (light) shell valve. Small scallops deposited an average of 0.55 stria per day, 0.42 stria per day, and 0.34 stria per day, respectively, during the 2-, 4-, and 6-wk experiments, whereas large scallops had a lower frequency of stria formation (0.20 stria per day, 0.18 stria per day, and 0.17 stria per day, respectively). Striae deposition and interstria distance were highly variable among small A. irradians. No relationship in interstria distance was obvious in A. irradians that deposited the same number of striae during 6 wk (0.45 striae per day) and held under conditions of high flow rate, indicating that stria formation is not synchronous with changes in the environment. Our results demonstrate unequivocally that in, A. irradians, stria formation is nondaily and is related to shell growth rate. The largest and oldest scallops (similar to 30 mm and 1.4 y old) formed striae at a rate of 0.17-0.2 stria per day whereas smaller and younger fast-growing A. irradians formed between 0.34 striae per day and 0.55 stria per day-clear evidence of nondaily and nonrhythmic deposition of striae in this pectinid species. Thus, striae cannot be used as a chronological marker with which environmental conditions can be compared

Predation of cockles (Cerastoderma edule) by the whelk (Buccinum undatum) under laboratory conditions

The feeding rate and behaviour of whelks (Buccinum undatum) offered cockles (Cerastoderma edule) in laboratory experiments were examined. When presented with cockles in a range of sizes (10–40 mm), 14 B. undatum (34.6–88.3 mm), held individually in aquaria, consumed a wide size range of cockles. Small whelks (\u3c40 \u3emm) consumed cockles (\u3c23 \u3emm), whereas large whelks, (\u3e60 mm) ate a greater number of larger cockles (\u3e30 mm) and a wider size range of cockles (12–40 mm) than smaller whelks. The majority (90%) of the shells of the predated cockles were undamaged and the few (B. undatum feeding on C. edule showed a method of attack that has not previously been reported and involved the use of the whelk\u27s foot to asphyxiate the cockle or to pull the shell valves apart. No filmed evidence was found for the previously reported shell ‘wedging’ technique for prising open the closed shell valves of C. edule, although 10% of the shells of consumed cockles in feeding experiments had damaged shell margins

Reconstructing North Atlantic marine climate variability using an absolutely-dated sclerochronological network

This is the final version of the article. Available from Elsevier via the DOI in this record.Reconstructing regional to hemispheric-scale climate variability requires the application of spatially representative and climatically sensitive proxy archives. Large spatial networks of dendrochronologies have facilitated the reconstruction of atmospheric variability and inferred variability in the Atlantic Ocean system. However, the marine environment has hitherto lacked the direct application of the spatial network approach because of the small number of individual absolutely-dated marine archives. In this study we present the first analyses of a network of absolutely-dated annually-resolved growth increment width chronologies from the marine bivalves Glycymeris glycymeris and Arctica islandica. The network contains eight chronologies spanning > 500 km along the western British continental shelf from the southern Irish Sea to North West Scotland. Correlation analysis of the individual chronologies and a suite of climate indices, including the Atlantic Multidecadal Oscillation (AMO), Central England surface air temperature (CET), northeast Atlantic sea surface temperatures (SST's) and the winter North Atlantic Oscillation (wNAO), demonstrates that, despite the large geographical distances been sites and the heterogeneous nature of the marine environment, the increment width variability in these series contains an element of coherence likely driven by a common response to changing environmental forcing. A nested Principal component analysis (PCA) was used to construct five composite series which explain between 31% and 74% of the variance across the individual chronologies. Linear regression analyses indicate that the composite series explain up to 41% of the variance in Northeast Atlantic SSTs over the calibration period (1975–2000). Calibration verification (reduction of error [RE] and coefficient of efficiency [CE]) statistics indicate that the composite series contains significant skill at reconstructing multi-decadal northeast Atlantic SST variability over the past two centuries (1805–2010). These data suggest that composite series derived from sclerochronology networks can facilitate the robust reconstruction of marine climate over past centuries to millennia providing invaluable baseline records of natural oceanographic variability.This work was supported financially by the NERC funded project Climate of the Last Millennium Project (CLAM; project No. NE/N001176/1) and the Marie Curie Frame work Partnership Annually Resolved Archives of Marine Climate Change (ARAMACC; Project No. FP7 604802). The authors would like to thank the three anonymous reviewer‘s for their constructive comments during the peer review process

Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.

Annually resolved North Atlantic marine climate over the last millennium

This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Owing to the lack of absolutely dated oceanographic information before the modern instrumental period, there is currently significant debate as to the role played by North Atlantic Ocean dynamics in previous climate transitions (for example, Medieval Climate Anomaly-Little Ice Age, MCA-LIA). Here we present analyses of a millennial-length, annually resolved and absolutely dated marine δ(18)O archive. We interpret our record of oxygen isotope ratios from the shells of the long-lived marine bivalve Arctica islandica (δ(18)O-shell), from the North Icelandic shelf, in relation to seawater density variability and demonstrate that solar and volcanic forcing coupled with ocean circulation dynamics are key drivers of climate variability over the last millennium. During the pre-industrial period (AD 1000-1800) variability in the sub-polar North Atlantic leads changes in Northern Hemisphere surface air temperatures at multi-decadal timescales, indicating that North Atlantic Ocean dynamics played an active role in modulating the response of the atmosphere to solar and volcanic forcing.We thank the members of the RV Bjarni Sæmundsson (Cruise No. B05-2006). This work was supported by the NERC-funded ULTRA project (Grant Number NE/H023356/1), NERC-funded CLAM project; (Project No. NE/N001176/1) and EU Millennium Project (Project number 017008). This study is a contribution to the Climate Change Consortium for Wales (C3W). We thank Brian Long (Bangor University) and Dr Julia Becker (Cardiff University) for their technical support, and Dr Manfred Mudelsee for his assistance with the trend analysis. We thank Dr Jessica Tierney and an anonymous reviewer for providing the constructive comments in the reviewing process

Reliability and validity of skin temperature measurement by telemetry thermistors and a thermal camera during exercise in the heat

Abstract. New technologies afford convenient modalities for skin temperature (T SKIN ) measurement, notably involving wireless telemetry and non-contact infrared thermometry. The purpose of this study was to investigate the validity and reliability of skin temperature measurements using a telemetry thermistor system (TT) and thermal camera (TC) during exercise in a hot environment. Each system was compared against a certified thermocouple, measuring the surface temperature of a metal block in a thermostatically controlled waterbath. Fourteen recreational athletes completed two incremental running tests, separated by one week. Skin temperatures were measured simultaneously with TT and TC compared against a hard-wired thermistor system (HW) throughout rest and exercise. Post hoc calibration based on waterbath results displayed good validity for TT (mean bias [MB] = -0.18°C, typical error [TE] = 0.18°C) and reliability (MB = -0.05°C, TE = 0.31°C) throughout rest and exercise. Poor validity (MB = -1.4°C, TE = 0.35°C) and reliability (MB = -0.65°C, TE = 0.52°C) was observed for TC, suggesting it may be best suited to controlled, static situations. These findings indicate TT systems provide a convenient, valid and reliable alternative to HW, useful for measurements in the field where traditional methods may be impractical

30 days wild: development and evaluation of a large-scale nature engagement campaign to improve well-being

There is a need to increase people’s engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro-nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature