New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Rapid quantification of microRNAs in plasma using a fast real time PCR system

The ability to rapidly detect circulating small RNAs, in particular microRNAs (miRNAs), would further increase their already established potential as biomarkers in a range of conditions. One rate-limiting factor is the time taken to perform quantitative real time PCR amplification. We therefore evaluated the ability of a novel thermal cycler to perform this step in less than 10 minutes. Quantitative PCR was performed on an xxpress® thermal cycler (BJS Biotechnologies, Perivale, UK), which employs a resistive heating system and forced air cooling to achieve thermal ramp rates of 10 °C/s, and a conventional peltier-controlled LightCycler 480 system (Roche, Basel, Switzerland) ramping at 4.8 °C/s. The threshold cycle (Ct) for detection of 18S rDNA from a standard genomic DNA sample was significantly more variable across the block (F-test, p=2.4x10-25) for the xxpress (20.01±0.47SD) than the LightCycler (19.87±0.04SD). RNA was extracted from human plasma, reverse transcribed and a panel of miRNAs amplified and detected using SYBR green (Kapa Biosystems, Wilmington, Ma, USA). The sensitivity of both systems was broadly comparable and both detected a panel of miRNAs reliably and indicated similar relative abundances. The xxpress thermal cycler facilitates rapid qPCR detection of small RNAs and brings point-of care diagnostics based upon circulating miRNAs a step closer to reality.

Development of a combined RT-PCR: NGS assay for microRNA biomarkers

The ability of miRNAs to act as diagnostic biomarkers could be expanded by availability of improved methodologies to detect and analyse these molecules. We have therefore developed an assay with the ability to selectively analyse pools of miRNAs, using the specificity of PCR to select targets and the power of NGS to reveal isomiRs of the chosen targets in a total assay time of two days.

The Cyrenaican Prehistory Project 2011: Late-Holocene environments and human activity from a cave fill in Cyrenaica, Libya

Little is known about late Holocene environmental change in Cyrenaica. The late Holocene sequence in the Haua Fteah, the key regional site, is highly discontinuous and characterised by stable-burning deposits. The geoarchaeology of the late-Holocene cave fill of a small cave, CP1565, located close to the Haua Fteah, is described. The well-stratified sequence, dating from the fourth century AD to the present day, provides a glimpse of life at the bottom of the settlement hierarchy and of changing environments over the last 1600 years, with degraded vegetation and aridity in the ‘Little Ice Age’.

Ca(2+) signals coordinate zygotic polarization and cell cycle progression in the brown alga Fucus serratus

Zygotes of the fucoid brown algae provide excellent models for addressing fundamental questions about zygotic symmetry breaking. Although the acquisition of polarity is tightly coordinated with the timing and orientation of the first asymmetric division-with zygotes having to pass through a G1/S-phase checkpoint before the polarization axis can be fixed -the mechanisms behind the interdependence of polarization and cell cycle progression remain unclear. In this study, we combine in vivo Ca(2+) imaging, single cell monitoring of S-phase progression and multivariate analysis of high-throughput intracellular Ca(2+) buffer loading to demonstrate that Ca(2+) signals coordinate polarization and cell cycle progression in the Fucus serratus zygote. Consistent with earlier studies on this organism, and in contrast to animal models, we observe no fast Ca(2+) wave following fertilization. Rather, we show distinct slow localized Ca(2+) elevations associated with both fertilization and S-phase progression, and we show that both S-phase and zygotic polarization are dependent on pre-S-phase Ca(2+) increases. Surprisingly, this Ca(2+) requirement cannot be explained by co-dependence on a single G1/ S-phase checkpoint, as S phase and zygotic polarization are differentially sensitive to pre-S-phase Ca(2+) elevations and can be uncoupled. Furthermore, subsequent cell cycle progression through M phase is independent of localized actin polymerization and zygotic polarization. This absence of a morphogenesis checkpoint, together with the observed Ca(2+)dependences of S phase and polarization, show that the regulation of zygotic division in the brown algae differs from that in other eukaryotic model systems, such as yeast and Drosophila.

The determinants of performance appraisal systems: A note (Do Brown and Heywood's results for Australia hold up for Britain?)

This article offers a replication for Britain of Brown and Heywood's analysis of the determinants of performance appraisal in Australia. Although there are some important limiting differences between our two datasets - the Australia Workplace Industrial Relations Survey (AWIRS) and the Workplace Employment Relations Survey (WERS) - we reach one central point of agreement and one intriguing shared insight. First, performance appraisal is negatively associated with tenure: where employers cannot rely on the carrot of deferred pay or the stick of dismissal to motivate workers, they will tend to rely more on monitoring, ceteris paribus. Second, employer monitoring and performance pay may be complementary. However, consonant with the disparate results from the wider literature, there is more modest agreement on the contribution of specific human resource management practices, and still less on the role of job control.

The Ectocarpus genome and the independent evolution of multicellularity in brown algae

Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related(1). These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae(2-5), closely related to the kelps(6,7) (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic(2) approaches to explore these and other(4,5) aspects of brown algal biology further.

Role of endoreduplication and apomeiosis during parthenogenetic reproduction in the model brown alga Ectocarpus

The filamentous brown alga Ectocarpus has a complex life cycle, involving alternation between independent and morphologically distinct sporophyte and gametophyte generations. In addition to this basic haploid–diploid life cycle, gametes can germinate parthenogenetically to produce parthenosporophytes. This article addresses the question of how parthenosporophytes, which are derived from a haploid progenitor cell, are able to produce meiospores in unilocular sporangia, a process that normally involves a reductive meiotic division.
We used flow cytometry, multiphoton imaging, culture studies and a bioinformatics survey of the recently sequenced Ectocarpus genome to describe its life cycle under laboratory conditions and the nuclear DNA changes which accompany key developmental transitions.
Endoreduplication occurs during the first cell cycle in about one-third of parthenosporophytes. The production of meiospores by these diploid parthenosporophytes involves a meiotic division similar to that observed in zygote-derived sporophytes. By contrast, meiospore production in parthenosporophytes that fail to endoreduplicate occurs via a nonreductive apomeiotic event.
Our results highlight Ectocarpus’s reproductive and developmental plasticity and are consistent with previous work showing that its life cycle transitions are controlled by genetic mechanisms and are independent of ploidy.

Cell cycles and endocycles in the model brown seaweed, Ectocarpus siliculosus

The recent announcement of the first genome sequence of a brown macroalga, the filamentous Ectocarpus, has been accompanied by a number of companion papers in New Phytologist. In a paper which contributes to this special issue, we classified the core cell cycle components of Ectocarpus, comparing them to the previously studied cell cycle components of diatoms. We then carried out fluorescence microscopy experiments to show that the Ectocarpus cell cycle could be deregulated during early development to give endopolyploid adults. We discuss here how our findings complement recent studies on endopolyploidy in plant and algal systems.

Epistolarum Familiarium Liber Unus in The Complete Works of John Milton: Volume XI (672pp.)

This edition of Milton’s Epistolarum Familiarium Liber Unus and of his Uncollected Letters, will appear as 672 pp. of The Complete Works of John Milton Volume XI, eds. Gordon Campbell and Edward Jones (Oxford University Press, forthcoming 2016). A diplomatic Latin text and a new facing English translation are complemented by a detailed Introduction and commentary that situate Milton’s Latin letters in relation to the classical, pedagogical and essentially humanist contexts at the heart of their composition. Now the art of epistolography advocated and exemplified by Cicero and Quintilian and embraced by Renaissance pedagogical manuals is read through a humanist filter whereby, via the precedent (and very title) of Epistolae Familiares, the Miltonic Liber is shown to engage with a neo-Latin re-invention of the classical epistola that had come to birth in quattrocento Italy in the letters of Petrarch and his contemporaries. At the same time the Epistolae are seen as offering fresh insight into Milton’s views on education, philology, his relations with Italian literati, his blindness, the poetic dimension of his Latin prose, and especially his verbal ingenuity as the ‘words’ of Latin ‘Letters’ become a self-conscious showcasing of etymological punning on the ‘letters’ of Latin ‘words’. The edition also announces several new discoveries, most notably its uncovering and collation of a manuscript of Henry Oldenburg’s transcription (in his Liber Epistolaris held in Royal Society, London) of Milton’s Ep. Fam. 25 (to Richard Jones). Oldenburg’s transcription (from the original sent to his pupil Jones) is an important find, given the loss of all but two of the manuscripts of Milton’s original Latin letters included in the 1674 volume. The edition also presents new evidence in regard to Milton’s relationships with the Italian philologist Benedetto Buonmattei, the Greek humanist Leonard Philaras, the radical pastor Jean Labadie (and the French church of London), and the elusive Peter Heimbach.