Evaluation of phylogenetic reconstruction methods using bacterial whole genomes: a simulation based study

Background: Phylogenetic reconstruction is a necessary first step in many analyses which use whole genome sequence data from bacterial populations. There are many available methods to infer phylogenies, and these have various advantages and disadvantages, but few unbiased comparisons of the range of approaches have been made. Methods: We simulated data from a defined "true tree" using a realistic evolutionary model. We built phylogenies from this data using a range of methods, and compared reconstructed trees to the true tree using two measures, noting the computational time needed for different phylogenetic reconstructions. We also used real data from Streptococcus pneumoniae alignments to compare individual core gene trees to a core genome tree. Results: We found that, as expected, maximum likelihood trees from good quality alignments were the most accurate, but also the most computationally intensive. Using less accurate phylogenetic reconstruction methods, we were able to obtain results of comparable accuracy; we found that approximate results can rapidly be obtained using genetic distance based methods. In real data we found that highly conserved core genes, such as those involved in translation, gave an inaccurate tree topology, whereas genes involved in recombination events gave inaccurate branch lengths. We also show a tree-of-trees, relating the results of different phylogenetic reconstructions to each other. Conclusions: We recommend three approaches, depending on requirements for accuracy and computational time. Quicker approaches that do not perform full maximum likelihood optimisation may be useful for many analyses requiring a phylogeny, as generating a high quality input alignment is likely to be the major limiting factor of accurate tree topology. We have publicly released our simulated data and code to enable further comparisons

Identifying and characterising key alternative splicing events in Drosophila development

In complex Metazoans a given gene frequently codes for multiple protein isoforms, through processes such as alternative splicing. Large scale functional annotation of these isoforms is a key challenge for functional genomics. This annotation gap is increasing with the large numbers of multi transcript genes being identified by technologies such as RNASeq. Furthermore attempts to characterise the functions of splicing in an organism are complicated by the difficulty in distinguishing functional isoforms from those produced by splicing errors or transcription noise. Tools to help prioritise candidate isoforms for testing are largely absent

On the Cretaceous origin of the Order Syracosphaerales and the genus Syracosphaera

New scanning electron microscope observations of unadulterated calcareous nannofossil assemblages on lamina surfaces of Cretaceous Tanzania Drilling Project sediments reveal high diversity in the < 3 μm size-range and high abundances of small and frangible morphologies. These assemblages prompt comparison to modern assemblages, which show similar high diversity and abundance of very small and fragile taxa, although these assemblages are generally not preserved in the fossil record due to taphonomic filtering. Not only are there broad similarities between the general composition of modern assemblages and those of the Tanzanian lagerstätte, but also our discovery of several new Cretaceous taxa provides evidence for greatly extended fossil lineages of extant orders, with implications for both deep-time biodiversity divergence and survival through the end-Cretaceous mass extinction. Our findings include: new species that are the first-recorded Mesozoic representatives of the extant Syracosphaeraceae and Papposphaeraceae; potentially previously unrecorded diversity in the Mesozoic Calciosoleniaceae, another extant order, represented by extant species that have been described already; and new species and unusually high abundances of the Mesozoic Stephanolithiaceae. We also highlight the extended range of an incertae sedis Cenozoic genus, Ellipsolithus, into at least the Turonian. Here, we describe seven new miniscule to very small Cretaceous species: Syracosphaera antiqua, S. repagula, Pocillithus macleodii, P. crucifer, Stradnerlithus wendleri, S.? haynesiae and Tortolithus foramen

New and intriguing calcareous nannofossils from the Turonian (Upper Cretaceous) of Tanzania

The preservation of exceptionally well-preserved, primary associations of calcareous nannofossils on lamina surfaces of shallowly-buried, uncemented, clay-rich Turonian sediments of coastal Tanzania has enabled us to document several intriguing new morphologies using the scanning electron microscope (SEM). Based on our new observations, we describe a new genus, Jimenezberrocosoia, and six new species, J. birchiae, Ellipsolithus linnertii, Petrarhabdus? kirenii, Braarudosphaera wendleriae, Nannoconus funiculus and Kokia kayae. We have also made two new combinations, Jimenezberrocosoia bosunensis (Jeremiah, 2001) and Nannoconus nicholasii (Lees, 2007), and emended the Order Braarudosphaerales to include the Nannoconaceae. Most of the taxa are illustrated with both SEM and light microscope images. The presence of Ellipsolithus in these Cretaceous sediments greatly extends the range of this formerly Cenozoic-restricted taxon

Evidence for global cooling in the Late Cretaceous

PublishedArticleThe Late Cretaceous ‘greenhouse’ world witnessed a transition from one of the warmest climates of the past 140 million years to cooler conditions, yet still without significant continental ice. Low-latitude sea surface temperature (SST) records are a vital piece of evidence required to unravel the cause of Late Cretaceous cooling, but high-quality data remain illusive. Here, using an organic geochemical palaeothermometer (TEX86), we present a record of SSTs for the Campanian–Maastrichtian interval (~83–66 Ma) from hemipelagic sediments deposited on the western North Atlantic shelf. Our record reveals that the North Atlantic at 35 °N was relatively warm in the earliest Campanian, with maximum SSTs of ~35 °C, but experienced significant cooling (~7 °C) after this to <~28 °C during the Maastrichtian. The overall stratigraphic trend is remarkably similar to records of high-latitude SSTs and bottom-water temperatures, suggesting that the cooling pattern was global rather than regional and, therefore, driven predominantly by declining atmospheric pCO2 levels.We gratefully acknowledge funding from the German Science Foundation (DFG Research Stipend Li 2177/1-1 to C.L.), a Royal Society (UK) URF (S.A.R.), a NERC (UK) grant (J.A.L.), a NERC (UK) studentship (K.L.), The Curry Fund of UCL (C.L.), the Cushman Foundation for Foraminiferal Research (J.M. Resig Fellowship to F.F.) and the Spanish Ministerio de Ciencia e Innovación project CGL2011-22912, co-financed by the European Regional Development Fund (I.P.-R., J.A.A., J.A.L.). We thank T. Dunkley-Jones and J. Young for assistance in collecting the samples and S. Schouten for providing TEX86L data from Demerara Rise. This paper is dedicated to Ernie Russell, who sadly died after submission of the manuscript

Diagnosing social anxiety in Parkinson’s disease: Characteristics and frequencies according to two diagnostic criteria

BACKGROUND: Studies found inconsistent frequencies of social anxiety disorder (SAD) in Parkinson’s disease (PD) (9.7%-50%). Previous reports did not test the impact of applying DSM-IV restrictive criteria that recommends the exclusion of secondary cases when diagnosing SAD in PD. OBJECTIVE: Our aim is to estimate the frequency of social anxiety according to DSM-IV criteria and according to an inclusive broader approach. Methods: One hundred and ten PD patients were assessed for the presence of SAD using SCID-I, diagnosis of social anxiety were determined according to two different criteria: following and not following DSM-IV recommendation for exclusion of cases though to be secondary to a general medical condition. RESULTS: SAD was present in 34 (31%) of patients, but 17 (15.5%) were secondary to a general medical condition. Patients with SAD were significantly younger, had earlier disease onset, had more severe PD symptoms, and were more frequently depressed. There was no difference in demographic and clinical features between primary and secondary SAD. DISCUSSION: We conclude that the use of different diagnostic criteria may have a massive impact in the estimation of frequency of SAD in PD

Species interactions regulate the collapse of biodiversity and ecosystem function in tropical forest fragments

Competitive interactions among species with similar ecological niches are known to regulate the assembly of biological communities. However, it is not clear whether such forms of competition can predict the collapse of communities and associated shifts in ecosystem function in the face of environmental change. Here, we use phylogenetic and functional trait data to test whether communities of two ecologically important guilds of tropical birds (frugivores and insectivores) are structured by species interactions in a fragmented Amazonian forest landscape. In both guilds, we found that forest patch size, quality, and degree of isolation influence the phylogenetic and functional trait structure of communities, with small, degraded, or isolated forest patches having an increased signature of competition (i.e., phylogenetic and functional trait overdispersion in relation to null models). These results suggest that local extinctions in the context of fragmentation are nonrandom, with a consistent bias toward more densely occupied regions of niche space. We conclude that the loss of biodiversity in fragmented landscapes is mediated by niche-based competitive interactions among species, with potentially far-reaching implications for key ecosystem processes, including seed dispersal and plant damage by phytophagous insects

Planktonic foraminiferal and calcareous nannofossil biostratigraphy and magnetostratigraphy of the uppermost Campanian and Maastrichtian at Zumaia, northern Spain

The well-exposed and continuous uppermost Cretaceous in the coastal section of Zumaia (northern Spain) crops out as cyclic, deep-water, hemipelagic carbonate-rich sediments of significant geological interest. We present a new, high-resolution calibration of planktonic foraminiferal and calcareous nannofossil biostratigraphic datums, alongside new magnetostratigraphy. Six planktonic foraminiferal zones (Rugoglobigerina rotundata to Pseudoguembelina hariaensis) and nine nannofossil (sub)zones (UC15eTP? to UC20dTP) have been identified, encompassing the uppermost Campanian through uppermost Maastrichtian. Magnetostratigraphic data were obtained from the lower half of the section, where chrons C31r and C31n have been identified; the lithological nature of the upper part of the section provided spurious palaeomagnetic results. According to these data, the Campanian/Maastrichtian (C/M) boundary lies in Chron C31r at Zumaia. Differences between the planktonic foraminiferal and nannofossil datums at Zumaia and those from the Tercis boundary stratotype section (France) suggest that the biostratigraphic criteria used to identify the C/M boundary are problematic. We propose, therefore, two alternative, key biostratigraphic datums with which to determine the stratigraphic position of this boundary: the stratigraphic base occurrence datum (BO) of the planktonic foraminifer Pseudoguembelina palpebra and the top occurrence datum (TO) of the nannofossil Broinsonia parca subsp. constricta. The C31r/C31n magnetic polarity reversal, and the BOs of the planktonic foraminifer Racemiguembelina fructicosa and the nannofossil Lithraphidites quadratus are events that may prove useful in formally defining the lower/upper Maastrichtian boundary

Effect of four-week cannabidiol treatment on cognitive function: secondary outcomes from a randomised clinical trial for the treatment of cannabis use disorder

RATIONALE: Chronic cannabis use is associated with impaired cognitive function. Evidence indicates cannabidiol (CBD) might be beneficial for treating cannabis use disorder. CBD may also have pro-cognitive effects; however, its effect on cognition in people with cannabis use disorder is currently unclear. OBJECTIVES: We aimed to assess whether a 4-week CBD treatment impacted cognitive function. We hypothesised that CBD treatment would improve cognition from baseline to week 4, compared to placebo. METHODS: Cognition was assessed as a secondary outcome in a phase 2a randomised, double-blind, parallel-group and placebo-controlled clinical trial of 4-week daily 200 mg, 400 mg and 800 mg CBD for the treatment of cannabis use disorder. Participants had moderate or severe DSM-5 cannabis use disorder and intended to quit cannabis use. Our pre-registered primary cognitive outcome was delayed prose recall. Secondary cognitive outcomes were immediate prose recall, stop signal reaction time, trail-making task performance, verbal fluency and digit span. RESULTS: Seventy participants were randomly assigned to placebo (n = 23), 400 mg CBD (n = 24) and 800 mg CBD (n = 23). A 200 mg group was eliminated from the trial because it was an inefficacious dose at interim analysis (n = 12) and was not analysed here. For the primary cognitive outcome, there was no effect of CBD compared to placebo, evidenced by a lack of dose-by-time interaction at 400 mg (0.46, 95%CIs: - 1.41, 2.54) and 800 mg (0.89, 95%CIs: - 0.99, 2.81). There was no effect of CBD compared to placebo on secondary cognitive outcomes, except backwards digit span which increased following 800 mg CBD (0.30, 95%CIs: 0.02, 0.58). CONCLUSIONS: In this clinical trial for cannabis use disorder, CBD did not influence delayed verbal memory. CBD did not have broad cognitive effects but 800 mg daily treatment may improve working memory manipulation. CLINICAL TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000,361-36)