Phylogenetic structure of the extinction and biotic factors explaining differential survival of terrestrial notosuchians at the Cretaceous–Palaeogene crisis

Although the clade Crocodylomorpha is represented by few extant species (Crocodylia), it has a rich fossil record. Hundreds of species, adapted to terrestrial, semi-aquatic and marine environments, have existed over more than 200 million years. Numerous studies have attempted to characterize the factors driving the diversification and extinction events of Crocodylomorpha, resulting in ambiguous and even contradictory conclusions, which points to the need for phylogenetically and temporally smaller-scaled studies. Here, we focus on differential survival at the Cretaceous–Palaeogene (K–Pg) crisis of Notosuchia, a diverse clade of mostly terrestrial Crocodylomorpha that achieved great diversity during the Cretaceous. More precisely, we tested the effect of body size and palaeotemperatures on notosuchian survival probability during the K–Pg crisis as well as the effect of diet on the evolution of their body size. We find that Notosuchia showed an evolutionary trend towards larger body sizes through time, associated with a shift from an omnivorous to a carnivorous diet. This may explain why sebecids were the only notosuchians to survive the K–Pg crisis. We also corroborate the conclusions of previous studies that detected a Lagerstätten effect occurring in the Adamantina Formation (Upper Cretaceous, Brazil, Bauru Group). This work confirms the value of more finely-scaled macroevolutionary studies for understanding the history of a rich and complex group such as Crocodylomorpha.     

A clinical return-to-work rule for patients with back pain

Background

Tools for early identification of workers with back pain who are at high risk of adverse occupational outcome would help concentrate clinical attention on the patients who need it most, while helping reduce unnecessary interventions (and costs) among the others. This study was conducted to develop and validate clinical rules to predict the 2-year work disability status of people consulting for nonspecific back pain in primary care settings.

Methods

This was a 2-year prospective cohort study conducted in 7 primary care settings in the Quebec City area. The study enrolled 1007 workers (participation, 68.4% of potential participants expected to be eligible) aged 18–64 years who consulted for nonspecific back pain associated with at least 1 day''s absence from work. The majority (86%) completed 5 telephone interviews documenting a large array of variables. Clinical information was abstracted from the medical files. The outcome measure was “return to work in good health” at 2 years, a variable that combined patients'' occupational status, functional limitations and recurrences of work absence. Predictive models of 2-year outcome were developed with a recursive partitioning approach on a 40% random sample of our study subjects, then validated on the rest.

Results

The best predictive model included 7 baseline variables (patient''s recovery expectations, radiating pain, previous back surgery, pain intensity, frequent change of position because of back pain, irritability and bad temper, and difficulty sleeping) and was particularly efficient at identifying patients with no adverse occupational outcome (negative predictive value 78%– 94%).

Interpretation

A clinical prediction rule accurately identified a large proportion of workers with back pain consulting in a primary care setting who were at a low risk of an adverse occupational outcome.Since the 1950s, back pain has taken on the proportions of a veritable epidemic, counting now among the 5 most frequent reasons for visits to physicians'' offices in North America^1,2,3 and ranking sixth among health problems generating the highest direct medical costs.⁴ Because of its high incidence and associated expense, effective intervention for back pain has great potential for improving population health and for freeing up extensive societal resources.So-called red flags to identify pain that is specific (i.e., pain in the back originating from tumours, fractures, infections, cauda equina syndrome, visceral pain and systemic disease)⁵ account for about 3% of all cases of back pain.⁶ The overwhelming majority of back-pain problems are thus nonspecific. One important feature of nonspecific back pain among workers is that a small proportion of cases (< 10%) accounts for most of the costs (> 70%).^{7,8,9,10,11,12,13,14} This fact has led investigators to focus on the early identification of patients who are at higher risk of disability, so that specialized interventions can be provided earlier, whereas other patients can be expected to recover with conservative care.^{9,15,16,17,18,19,20,21,22,23,24,25} Although this goal has become much sought-after in back-pain research, most available studies in this area have 3 methodological problems:

• Potential predictors are often limited to administrative or clinical data, whereas it is clear that back pain is a multidimensional health problem.
• The outcome variable is most often a 1-point dichotomous measure of return to work, time off work or duration of compensation, although some authors have warned against the use of first return to work as a measure of recovery. Baldwin and colleagues,²⁶ for instance, point out that first return to work is frequently followed by recurrences of work absence.
• Most published prediction rules developed for back pain have not been successfully validated on any additional samples of patients.

Our study aimed to build a simple predictive tool that could be used by primary care physicians to identify workers with nonspecific back pain who are at higher risk of long-term adverse occupational outcomes, and then to validate this tool on a fresh sample of subjects.     

Differential Phosphorylation of Smad1 Integrates BMP and Neurotrophin Pathways through Erk/Dusp in Axon Development

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X-ray diffraction characterization of the dense phases formed by nucleosome core particles

Multiple dense phases of nucleosome core particles (NCPs) were formed in controlled ionic conditions (15-160 mM monovalent salt, no divalent ions), under osmotic pressures ranging from 4.7 x 10(5) to 2.35 x 10(6) Pa. We present here the x-ray diffraction analysis of these phases. In the lamello-columnar phase obtained at low salt concentration (<25 mM), NCPs stack into columns that align to form bilayers, kept separated from one another by a layer of solvent. NCPs form a monoclinic lattice in the plane of the bilayer. For high salt concentration (>50 mM), NCPs order into either a two-dimensional columnar hexagonal phase or into three-dimensional orthorhombic (quasi-hexagonal) crystals. The lamellar and hexagonal (or quasi-hexagonal) organizations coexist in the intermediate salt range; their demixing requires a long time. For an applied pressure P = 4.7 10(5) Pa, the calculated NCPs concentration ranges from approximately 280 to 320 mg/ml in the lamello-columnar phase to 495 to 585 mg/ml in the three-dimensional orthorhombic phase. These concentrations cover the concentration of the living cell.     

Protein oligomerization mediated by the transmembrane carboxyl terminal domain of Bcl-XL

Bcl-XL is a pro-survival member of the Bcl-2 family that can be found in the outer mitochondrial membrane and in soluble cytosolic homodimers. Bcl-XL can bind pro-apoptotic members of this family preventing them from activating the execution phase of apoptosis. Bcl-XL has been shown to homodimerize in different ways, although most binding and structural assays have been carried out in the absence of its carboxyl terminal transmembrane domain. We show here that this domain can by itself direct protein oligomerization, which could be related to its previously reported role in mitochondrial morphology alterations and apoptosis inhibition.     

Conservation of key members in the course of the evolution of the insulin signaling pathway

Our understanding of the evolution of the insulin signaling pathway (ISP) is still incomplete. One intriguing unanswered question is the explanation of the emergence of the glucostatic role of insulin in mammals. To find out whether this is due to the development of new sets of signaling transduction elements in these organisms, or to the establishment of new interactions between pre-existing proteins, we rebuilt putative orthologous ISPs in 17 eukaryotic organisms. Then, we computed the conservation of orthologous ISPs at different levels, from sequence similarity of orthologous proteins to co-evolution of interacting domains. We found that the emergence of glucostatic role in mammals can neither be explained by the development of new sets of signaling elements, nor by the establishment of new interactions between pre-existing proteins. The comparison of orthologous IRS molecules indicates that only in mammals have they acquired their complete functionality as efficient recruiters of effector sub-pathways.     

Inulavosin and its benzo‐derivatives,melanogenesis inhibitors,target the copper loading mechanism to the active site of tyrosinase

Tyrosinase, a melanosomal membrane protein containing copper, is a key enzyme for melanin synthesis in melanocytes. Inulavosin inhibits melanogenesis by enhancing a degradation of tyrosinase in lysosomes. However, the mechanism by which inulavosin redirects tyrosinase to lysosomes is yet unknown. The analyses of structure–activity relationship of inulavosin and its benzo‐derivatives reveal that the hydroxyl and the methyl groups play a critical role in their inhibitory activity. Intriguingly, the docking studies to tyrosinase suggest that the compounds showing inhibitory activity bind through hydrophobic interactions to the cavity of tyrosinase below which the copper‐binding sites are located. This cavity is proposed to be required for the association with a chaperon that assists in copper loading to tyrosinase in Streptomyces antibioticus. Inulavosin and its benzo‐derivatives may compete with the copper chaperon and result in a lysosomal mistargeting of apo‐tyrosinase that has a conformational defect.     

Chloroplast nitrite uptake is enhanced in Arabidopsis PII mutants

In higher plants, the PII protein is a nuclear-encoded plastid protein that regulates the activity of a key enzyme of arginine biosynthesis. We have previously observed that Arabidopsis PII mutants are more sensitive to nitrite toxicity. Using intact chloroplasts isolated from Arabidopsis leaves and (15)N-labelled nitrite we show that a light-dependent nitrite uptake into chloroplasts is increased in PII knock-out mutants when compared to the wild-type. This leads to a higher incorporation of (15)N into ammonium and amino acids in the mutant chloroplasts. However, the uptake differences do not depend on GS/GOGAT activities. Our observations suggest that PII is involved in the regulation of nitrite uptake into higher plant chloroplasts.     

Effects of mechanical stress on Anammox granules in a sequencing batch reactor (SBR)

The effect of shear stress on Anammox process was studied in a sequencing batch reactor (SBR). The reactor was operated during 218 days under different stirring speeds (60-250 rpm) in order to expose the system to different shear conditions and to study the stability of the Anammox granules referred to their biological activity and size. The nitrogen loading rate (NLR) fed to the SBR was kept around 0.3g N(L day)(-1). The nitrite (limiting substrate) removal percentage was 98% during most of the operational period. The specific Anammox activity of the biomass was practically constant and around 0.4 g N(g VSSday)(-1) and the average feret diameter of the formed granules was 0.64 mm. Obtained results indicated that stirring speeds up to 180 rpm have no negative effect on the performance of the Anammox process, whereas Anammox activity decreased to 40% when a rotating speed of 250 rpm was tested and the average diameter decreased in 45%, the concentration of solids in the effluent increased to 0.2g TSSL(-1) and nitrite was accumulated in the reactor up to 60 mg NL(-1).