Near-stasis in the long-term diversification of Mesozoic tetrapods

How did evolution generate the extraordinary diversity of vertebrates on land? Zero species are known prior to ~380 million years ago, and more than 30,000 are present today. An expansionist model suggests this was achieved by large and unbounded increases, leading to substantially greater diversity in the present than at any time in the geological past. This model contrasts starkly with empirical support for constrained diversification in marine animals, suggesting different macroevolutionary processes on land and in the sea. We quantify patterns of vertebrate standing diversity on land during the Mesozoic–early Paleogene interval, applying sample-standardization to a global fossil dataset containing 27,260 occurrences of 4,898 non-marine tetrapod species. Our results show a highly stable pattern of Mesozoic tetrapod diversity at regional and local levels, underpinned by a weakly positive, but near-zero, long-term net diversification rate over 190 million years. Species diversity of non-flying terrestrial tetrapods less than doubled over this interval, despite the origins of exceptionally diverse extant groups within mammals, squamates, amphibians, and dinosaurs. Therefore, although speciose groups of modern tetrapods have Mesozoic origins, rates of Mesozoic diversification inferred from the fossil record are slow compared to those inferred from molecular phylogenies. If high speciation rates did occur in the Mesozoic, then they seem to have been balanced by extinctions among older clades. An apparent 4-fold expansion of species richness after the Cretaceous/Paleogene (K/Pg) boundary deserves further examination in light of potential taxonomic biases, but is consistent with the hypothesis that global environmental disturbances such as mass extinction events can rapidly adjust limits to diversity by restructuring ecosystems, and suggests that the gradualistic evolutionary diversification of tetrapods was punctuated by brief but dramatic episodes of radiation.27 page(s

Climate constrains the evolutionary history and biodiversity of crocodylians

The fossil record of crocodylians and their relatives (pseudosuchians) reveals a rich evolutionary history, prompting questions about causes of long-term decline to their present-day low biodiversity. We analyse climatic drivers of subsampled pseudosuchian biodiversity over their 250 million year history, using a comprehensive new data set. Biodiversity and environmental changes correlate strongly, with long-term decline of terrestrial taxa driven by decreasing temperatures in northern temperate regions, and biodiversity decreases at lower latitudes matching patterns of increasing aridification. However, there is no relationship between temperature and biodiversity for marine pseudosuchians, with sea-level change and post-extinction opportunism demonstrated to be more important drivers. A ‘modern-type' latitudinal biodiversity gradient might have existed throughout pseudosuchian history, and range expansion towards the poles occurred during warm intervals. Although their fossil record suggests that current global warming might promote long-term increases in crocodylian biodiversity and geographic range, the 'balancing forces' of anthropogenic environmental degradation complicate future predictions

Productivity, niche availability, species richness, and extinction risk: Untangling relationships using individual-based simulations

It has often been suggested that the productivity of an ecosystem affects the number of species that it can support. Despite decades of study, the nature, extent, and underlying mechanisms of this relationship are unclear. One suggested mechanism is the “more individuals” hypothesis (MIH). This proposes that productivity controls the number of individuals in the ecosystem, and that more individuals can be divided into a greater number of species before their population size is sufficiently small for each to be at substantial risk of extinction. Here, we test this hypothesis using REvoSim: an individual-based eco-evolutionary system that simulates the evolution and speciation of populations over geological time, allowing phenomena occurring over timescales that cannot be easily observed in the real world to be evaluated. The individual-based nature of this system allows us to remove assumptions about the nature of speciation and extinction that previous models have had to make. Many of the predictions of the MIH are supported in our simulations: Rare species are more likely to undergo extinction than common species, and species richness scales with productivity. However, we also find support for relationships that contradict the predictions of the strict MIH: species population size scales with productivity, and species extinction risk is better predicted by relative than absolute species population size, apparently due to increased competition when total community abundance is higher. Furthermore, we show that the scaling of species richness with productivity depends upon the ability of species to partition niche space. Consequently, we suggest that the MIH is applicable only to ecosystems in which niche partitioning has not been halted by species saturation. Some hypotheses regarding patterns of biodiversity implicitly or explicitly overlook niche theory in favor of neutral explanations, as has historically been the case with the MIH. Our simulations demonstrate that niche theory exerts a control on the applicability of the MIH and thus needs to be accounted for in macroecology

Localisation of an occult thyrotropinoma with 11^{11}C-methionine PET-CT before and after somatostatin analogue therapy

A 75-year-old woman presented to her local endocrine service with tiredness, palpitations, and enlargement of a longstanding goitre. Unexpectedly, her thyrotropin (thyroid-stimulating hormone [TSH]) concentration was not suppressed (6·3 mU/L; reference range 0·35–5·5) despite raised concentrations of thyroid hormones (free thyroxine [T$_{4}$] 89·1 pmol/L [reference range 10–19·8]; free triiodothyronine [T$_{3}$] 11·7 pmol/L [3·0–6·5]). After exclusion of laboratory assay interference, a thyrotropin-releasing hormone test showed an attenuated response (TSH at 0 min was 6·1 mU/L, at 20 min was 6·8 mU/L, and at 60 min was 8·5 mU/L), raising suspicion of a thyrotropinoma (also known as TSHoma). However, pituitary MRI was normal. The patient was referred to our centre for further assessment. On repeat MRI, the pituitary gland showed mild asymmetry (right larger than left; figure A). Functional imaging with 11C-methionine ($^{11}$C-Met) PET-CT revealed intense tracer uptake (denoting active peptide synthesis) on the right side of the sella (red hot spot in figure A). Treatment with a depot somatostatin analogue (SSA) led to resolution of symptoms and normalisation of thyroid function (TSH 0·6 mU/L, free T$_{4}$ 12·5 pmol/L, and free T$_{3}$ 3·8 pmol/L). Repeat $^{11}$C-Met PET-CT showed absence of the right-sided focal hot spot (figure B). 14 months into treatment, the patient had several hypoglycaemic episodes, which resolved after discontinuation of SSA. However, thyrotoxicosis recurred (TSH 4·3 mU/L, free T$_{4}$ 38·1 pmol/L, free T$_{3}$ 11·6 pmol/L), and repeat $^{11}$C-Met PET-CT revealed the reappearance of the right-sided hot spot (figure C). During pituitary surgery, a microthyrotropinoma was resected from the right side of the gland (figure D). The patient remains in clinical and biochemical remission more than 12 months after surgery and has normal pituitary function

RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

New MR sequences in daily practice: susceptibility weighted imaging. A pictorial essay

Background Susceptibility-weighted imaging (SWI) is a relatively new magnetic resonance (MR) technique that exploits the magnetic susceptibility differences of various tissues, such as blood, iron and calcification, as a new source of contrast enhancement. This pictorial review is aimed at illustrating and discussing its main clinical applications. Methods SWI is based on high-resolution, threedimensional (3D), fully velocity-compensated gradientecho sequences using both magnitude and phase images. A phase mask obtained from the MR phase images is multiplied with magnitude images in order to increase the visualisation of the smaller veins and other sources of susceptibility effects, which are displayed at best after postprocessing of the 3D dataset with the minimal intensity projection (minIP) algorithm. Results SWI is very useful in detecting cerebral microbleeds in ageing and occult low-flow vascular malformations, in characterising brain tumours and degenerative diseases of the brain, and in recognizing calcifications in various pathological conditions. The phase images are especially useful in differentiating between paramagnetic susceptibility effects of blood and diamagnetic effects of calcium. SWI can also be used to evaluate changes in iron content in different neurodegenerative disorders. Conclusion SWI is useful in differentiating and characterising diverse brain disorders

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Climate-mediated diversification of turtles in the Cretaceous

The file attached is the published version of the article