Elbow-joint morphology in the North American 'cheetah-like' cat Miracinonyx trumani.

The North American cheetah-like cat Miracinonyx trumani is an extinct species that roamed the Pleistocene prairies 13 000 years ago. Although M. trumani is more closely related to the cougar (Puma concolor) than to the living cheetah (Acinonyx jubatus), it is believed that both A. jubatus and M. trumani possess a highly specialized skeleton for fast-running, including limbs adapted for speed at the expense of restricting the ability of prey grappling. However, forelimb dexterity of M. trumani has not been yet investigated. Here, we quantify the 3D-shape of the humerus distal epiphysis as a proxy for elbow-joint morphology in a sample of living cats to determine whether the extinct M. trumani was specialized to kill open-country prey using predatory behaviour based on fast running across the prairies and steppe terrains of the North American Pleistocene. We show that M. trumani had an elbow morphology intermediate to that of P. concolor and A. jubatus, suggesting that M. trumani had a less specialized pursuit predatory behaviour than A. jubatus. We propose that M. trumani probably deployed a unique predatory behaviour without modern analogues. Our results bring into question the degree of ecomorphological convergence between M. trumani and its Old World vicar A. jubatus.

The brain of the North American cheetah-like cat Miracinonyx trumani.

The cheetah Acinonyx jubatus, the fastest living land mammal, is an atypical member of the family Felidae. The extinct feline Miracinonyx trumani, known as the North American cheetah, is thought to have convergently evolved with Acinonyx to pursue fast and open-country prey across prairies and steppe environments of the North American Pleistocene. The brain of Acinonyx is unique among the living felids, but it is unknown whether the brain of the extinct M. trumani is convergent to that of Acinonyx. Here, we investigate the brain of M. trumani from a cranium endocast, using a comparative sample of other big cats. We demonstrate that the brain of M. trumani was different from that of the living A. jubatus. Indeed, its brain shows a unique combination of traits among living cats. This suggests that the case of extreme convergence between Miracinonyx and its living Old World vicar should be reconsidered.

Serial disparity in the carnivoran backbone unveils a complex adaptive role in metameric evolution.

Organisms comprise multiple interacting parts, but few quantitative studies have analysed multi-element systems, limiting understanding of phenotypic evolution. We investigate how disparity of vertebral morphology varies along the axial column of mammalian carnivores - a chain of 27 subunits - and the extent to which morphological variation have been structured by evolutionary constraints and locomotory adaptation. We find that lumbars and posterior thoracics exhibit high individual disparity but low serial differentiation. They are pervasively recruited into locomotory functions and exhibit relaxed evolutionary constraint. More anterior vertebrae also show signals of locomotory adaptation, but nevertheless have low individual disparity and constrained patterns of evolution, characterised by low-dimensional shape changes. Our findings demonstrate the importance of the thoracolumbar region as an innovation enabling evolutionary versatility of mammalian locomotion. Moreover, they underscore the complexity of phenotypic macroevolution of multi-element systems and that the strength of ecomorphological signal does not have a predictable influence on macroevolutionary outcomes.

Phenotypic integration in the carnivoran backbone and the evolution of functional differentiation in metameric structures.

Explaining the origin and evolution of a vertebral column with anatomically distinct regions that characterizes the tetrapod body plan provides understanding of how metameric structures become repeated and how they acquire the ability to perform different functions. However, despite many decades of inquiry, the advantages and costs of vertebral column regionalization in anatomically distinct blocks, their functional specialization, and how they channel new evolutionary outcomes are poorly understood. Here, we investigate morphological integration (and how this integration is structured [modularity]) between all the presacral vertebrae of mammalian carnivorans to provide a better understanding of how regionalization in metameric structures evolves. Our results demonstrate that the subunits of the presacral column are highly integrated. However, underlying to this general pattern, three sets of vertebrae are recognized as presacral modules-the cervical module, the anterodorsal module, and the posterodorsal module-as well as one weakly integrated vertebra (diaphragmatic) that forms a transition between both dorsal modules. We hypothesize that the strength of integration organizing the axial system into modules may be associated with motion capability. The highly integrated anterior dorsal module coincides with a region with motion constraints to avoid compromising ventilation, whereas for the posterior dorsal region motion constraints avoid exceeding extension of the posterior back. On the other hand, the weakly integrated diaphragmatic vertebra belongs to the "Diaphragmatic joint complex"-a key region of the mammalian column of exceedingly permissive motion. Our results also demonstrate that these modules do not match with the traditional morphological regions, and we propose natural selection as the main factor shaping this pattern to stabilize some regions and to allow coordinate movements in others.

Photoelectrochemical Behavior and Computational Insights for Pristine and Doped NdFeO3 Thin-Film Photocathodes.

Among the different strategies that are being developed to solve the current energy challenge, harvesting energy directly from sunlight through a tandem photoelectrochemical cell (water splitting) is most attractive. Its implementation requires the development of stable and efficient photocathodes, NdFeO3 being a suitable candidate among ternary oxides. In this study, transparent NdFeO3 thin-film photocathodes have been successfully prepared by a citric acid-based sol-gel procedure, followed by thermal treatment in air at 640 °C. These electrodes show photocurrents for both the hydrogen evolution and oxygen reduction reactions. Doping with Mg2+ and Zn2+ has been observed to significantly enhance the photoelectrocatalytic performance of NdFeO3 toward oxygen reduction. Magnesium is slightly more efficient as a dopant than Zn, leading to a multiplication of the photocurrent by a factor of 4-5 for a doping level of 5 at % (with respect to iron atoms). This same trend is observed for hydrogen evolution. The beneficial effect of doping is primarily attributed to an increase in the density and a change in the nature of the majority charge carriers. DFT calculations help to rationalize the behavior of NdFeO3 by pointing to the importance of nanostructuring and doping. All in all, NdFeO3 has the potential to be used as a photocathode in photoelectrochemical applications, although efforts should be directed to limit surface recombination.

The Medicago truncatula Yellow Stripe1-Like3 gene is involved in vascular delivery of transition metals to root nodules.

Symbiotic nitrogen fixation carried out in legume root nodules requires transition metals. These nutrients are delivered by the host plant to the endosymbiotic nitrogen-fixing bacteria living within the nodule cells, a process in which vascular transport is essential. As members of the Yellow Stripe-Like (YSL) family of metal transporters are involved in root to shoot transport, they should also be required for root to nodule metal delivery. The genome of the model legume Medicago truncatula encodes eight YSL proteins, four of them with a high degree of similarity to Arabidopsis thaliana YSLs involved in long-distance metal trafficking. Among them, MtYSL3 is a plasma membrane protein expressed by vascular cells in roots and nodules and by cortical nodule cells. Reducing the expression level of this gene had no major effect on plant physiology when assimilable nitrogen was provided in the nutrient solution. However, nodule functioning was severely impaired, with a significant reduction of nitrogen fixation capabilities. Further, iron and zinc accumulation and distribution changed. Iron was retained in the apical region of the nodule, while zinc became strongly accumulated in the nodule veins in the ysl3 mutant. These data suggest a role for MtYSL3 in vascular delivery of iron and zinc to symbiotic nitrogen fixation.

Morphological evolution of the carnivoran sacrum.

The sacrum is a key piece of the vertebrate skeleton, since it connects the caudal region with the presacral region of the vertebral column and the hind limbs through the pelvis. Therefore, understanding its form and function is of great relevance in vertebrate ecomorphology. However, it is striking that morphometric studies that quantify its morphological evolution in relation to function are scarce. The main goal of this study is to investigate the morphological evolution of the sacrum in relation to its function in the mammalian order Carnivora, using three-dimensional (3D) geometric morphometrics. Principal component analysis under a phylogenetic background indicated that changes in sacrum morphology are mainly focused on the joint areas where it articulates with other parts of the skeleton allowing resistance to stress at these joints caused by increasing muscle loadings. In addition, we demonstrated that sacrum morphology is related to both the length of the tail relativised to the length of the body, and the length of the body relativised to body mass. We conclude that the sacrum in carnivores has evolved in response to the locomotor requirements of the species analysed, but in locomotion, each family has followed alternative morphological solutions to address the same functional demands.

Biomechanical simulations reveal a trade-off between adaptation to glacial climate and dietary niche versatility in European cave bears.

The cave bear is one of the best known extinct large mammals that inhabited Europe during the "Ice Age," becoming extinct ≈24,000 years ago along with other members of the Pleistocene megafauna. Long-standing hypotheses speculate that many cave bears died during their long hibernation periods, which were necessary to overcome the severe and prolonged winters of the Last Glacial. Here, we investigate how long hibernation periods in cave bears would have directly affected their feeding biomechanics using CT-based biomechanical simulations of skulls of cave and extant bears. Our results demonstrate that although large paranasal sinuses were necessary for, and consistent with, long hibernation periods, trade-offs in sinus-associated cranial biomechanical traits restricted cave bears to feed exclusively on low energetic vegetal resources during the predormancy period. This biomechanical trade-off constitutes a new key factor to mechanistically explain the demise of this dominant Pleistocene megafaunal species as a direct consequence of climate cooling.

Taking a look into the orbit of mammalian carnivorans.

In this study, we explore the relationship between orbit anatomy and different ecological factors in carnivorous mammals from a phylogenetic perspective. We calculated the frontation (α), convergence (ß), and orbitotemporal (Ω) angles of the orbit from 3D coordinates of anatomical landmarks in a wide sample of carnivores with different kinds of visual strategy (i.e. photopic, scotopic, and mesopic), habitat (i.e. open, mixed, and closed), and substrate use (i.e. arboreal, terrestrial, and aquatic). We used Bloomberg's K and Pagel's λ to assess phylogenetic signal in frontation, convergence, and orbitotemporal angles. The association of orbit orientation with skull length and ecology was explored using phylogenetic generalized least squares and phylogenetic manova, respectively. Moreover, we also computed phylomorphospaces from orbit orientation. Our results indicate that there is not a clear association between orbit orientation and the ecology of living carnivorans. We hypothesize that the evolution of the orbit in mammalian carnivores represents a new case of an ecological bottleneck specific to carnivorans. New directions for future research are discussed in light of this new evidence.

Dental caries in the fossil record: a window to the evolution of dietary plasticity in an extinct bear.

During the late Pleistocene of North America (≈36,000 to 10,000 years ago), saber-toothed cats, American lions, dire wolves, and coyotes competed for prey resources at Rancho La Brea (RLB). Despite the fact that the giant short-faced bear (Arctodus simus) was the largest land carnivoran present in the fauna, there is no evidence that it competed with these other carnivores for prey at the site. Here, for the first time, we report carious lesions preserved in specimens of A. simus, recovered from RLB. Our results suggest that the population of A. simus from RLB was more omnivorous than the highly carnivorous populations from the Northwest. This dietary variation may be a consequence of different competitive pressures.

Experimental efficacy of anidulafungin against Aspergillus terreus species complex.

Whereas echinocandins are alternatives for the treatment of invasive aspergillosis, the efficacy of anidulafungin (AFG) against Aspergillus terreus infection has not yet been explored. We have evaluated the in vitro activity, as well as the in vivo efficacy of AFG in neutropenic mice infected by A. terreus species complex. Time-kill studies showed in vitro fungistatic activity of AFG against two strains. AFG at doses of 5 and 10 mg/kg/day significantly reduced the fungal load in kidney of mice, but only the higher dose was able to prolong survival.

Influence of CYP2C19 polymorphisms in platelet reactivity and prognosis in an unselected population of non ST elevation acute coronary syndrome.

INTRODUCTION AND OBJECTIVES: CYP2C19*2 and CYP2C19*17 alleles appear to contribute to heterogeneous clopidogrel metabolism. The aims of the present study were to assess the phenotype-genotype relationship of CYP2C19*2 and *17 allele carriage and to explore the clinical impact of those polymorphisms at 6-month follow-up of an acute event in an unselected population of non-ST elevation acute coronary syndrome. METHODS: Recruitment for the first and second objectives was 40 stable acute coronary syndrome patients under dual antiplatelet therapy at 12 months after coronary stent placement and an unselected population of 493 consecutive patients with non-ST elevation acute coronary syndrome, respectively. Platelet reactivity was assessed by optical aggregometry induced by adenosine diphosphate and thrombin receptor activating peptide, and by vasodilator-stimulated phosphoprotein phosphorylation measurement using flow cytometry. Genotypes were determined with a TaqMan assay. RESULTS: Only the vasodilator-stimulated phosphoprotein phosphorylation measurement detected significant differences in on-clopidogrel platelet reactivity between the wild-type subjects and the CYP2C19*2 (P=.020) and *17 allele carriers (P=.048). No significant difference was found between CYP2C19*2 ([HR (95%CI): 1 (0.94-1.55)], P=.984) or *17 ([HR (95%CI): 0.93 (0.61-1.43)], P=.753) allele carriage and the occurrence of adverse events at 6-month follow-up. CONCLUSIONS: Even though CYP2C19 genotype is associated with variable on-clopidogrel platelet reactivity, it has no significant clinical influence. Prognosis of acute coronary syndromes may be influenced by a myriad of variables.

Ventricular arrhythmias in Chronic Chagas' Myocardiopathy: a case report and brief review of different antiarrhythmic strategies.

Management of ventricular arrhythmias due to Chronic Chagas' Myocardiopathy (CCM) is challenging. We present a case of CCM complicated with ventricular tachycardia (VT), and a brief review focused on VT management in this occidental emergent entity.

Increased major bleeding complications related to triple antithrombotic therapy usage in patients with atrial fibrillation undergoing percutaneous coronary artery stenting.

BACKGROUND: The optimal antithrombotic therapy strategy for atrial fibrillation (AF) patients who undergo percutaneous coronary intervention with stent implantation (PCI-S) is unknown. We assessed the safety of antithrombotic therapy strategies in AF patients with indication for oral anticoagulation (OAC) undergoing PCI-S. METHODS: We studied consecutive AF patients with indication for OAC who underwent PCI-S. We compared patients that received triple antithrombotic therapy (TT) [aspirin, clopidogrel, and coumadin] against other regimes (non-TT) after PCI-S. The primary end point was defined as the occurrence of major bleeding complications that were termed as early major bleeding (EMB) [< or = 48 h] or late major bleeding (LMB) [> 48 h]. Clinical follow-up was performed, and complications were recorded. RESULTS: We studied 104 patients (mean age +/- SD, 72 +/- 8 years; 70% men); TT was used in 51 patients (49%). TT was associated with a higher incidence of LMB (21.6% vs non-TT, 3.8%; p = 0.006) but not of EMB (5.8% vs non-TT, 11.3%; p = 0.33). In multivariate analyses, glycoprotein (GP) IIb/IIIa inhibitor use (hazard ratio [HR], 13.5; 95% confidence interval [CI], 1.7 to 108.3; p = 0.014) and PCI-S of three vessels or left main artery disease (HR, 7.9; 95% CI, 1.6 to 39.2; p = 0.01) were independent predictors for EMB. TT use (HR, 7.1; 95% CI, 1.5 to 32.4; p = 0.012), the occurrence of EMB (HR, 6.7; 95% CI, 1.8 to 25.3; p = 0.005), and baseline anemia (HR, 3.8; 95% CI, 1.2 to 12.5; p = 0.027) were independent predictors for LMB. No differences in major cardiovascular events were observed in patients treated with TT vs non-TT (25.5% vs 21.0%; p = 0.53). CONCLUSION: A high rate of major bleeding is observed in AF patients with indication for OAC undergoing PCI-S who receive TT. GP IIb/IIIa inhibitor use and multivessel/left main artery disease during PCI-S were independent predictors for EMB, while TT use, occurrence of EMB, and baseline anemia were independent predictors for LMB.

Efficacy of liposomal amphotericin B in treatment of systemic murine fusariosis.

We have compared the activities of liposomal amphotericin B (LAMB) at 3, 5, 10, and 20 mg/kg/day and amphotericin B deoxycholate (AMB) at 1.5 and 2.5 mg/kg/day in a murine systemic infection by Fusarium verticillioides. Survival was improved by all treatments except AMB at 1.5 mg/kg/day. The tissue burden in liver was reduced by LAMB at all dosages and by AMB at 2.5 mg/kg/day. The two highest dosages of LAMB showed significant reductions in the spleen.