Computational assessment of lipid production in Rhodosporidium toruloides in two-stage and one-stage batch bioprocesses.

Oleaginous yeasts are promising platforms for microbial lipids production as a renewable and sustainable alternative to vegetable oils in biodiesel production. In this paper, a thorough in silico assessment of lipid production in batch cultivation by Rhodosporidium toruloides was developed. By means of dynamic flux balance analysis, the traditional two-stage bioprocess (TSB) performed by the native strain was contrasted with one-stage bioprocess (OSB) using four designed strains obtained by gene knockout strategies. Lipid titer, yield, content, and productivity were analyzed at different initial C/N ratios as relevant performance indicators used in bioprocesses. By weighting these indicators, a global lipid efficiency metric (GLEM) was defined to consider different scenarios. Under simulated conditions, designed strains for lipid overproduction in OSB outperformed the TSB in terms of lipid title (up to threefold), lipid yield (up to 2.4-fold), lipid content (up to 2.8-fold, with a maximum of 76%), and productivity (up to 1.3-fold), depending on C/N ratios. Using these efficiency parameters and the proposed GLEM, the process of selecting the most suitable candidates for lipid production could be carried out before experimental assays. This methodology holds the potential to be extended to other oleaginous microorganisms and diverse strain design techniques.

When adaptive radiations collide: Different evolutionary trajectories between and within island and mainland lizard clades.

Oceanic islands are known as test tubes of evolution. Isolated and colonized by relatively few species, islands are home to many of nature's most renowned radiations from the finches of the Galápagos to the silverswords of the Hawaiian Islands. Despite the evolutionary exuberance of insular life, island occupation has long been thought to be irreversible. In particular, the presumed much tougher competitive and predatory milieu in continental settings prevents colonization, much less evolutionary diversification, from islands back to mainlands. To test these predictions, we examined the ecological and morphological diversity of neotropical Anolis lizards, which originated in South America, colonized and radiated on various islands in the Caribbean, and then returned and diversified on the mainland. We focus in particular on what happens when mainland and island evolutionary radiations collide. We show that extensive continental radiations can result from island ancestors and that the incumbent and invading mainland clades achieve their ecological and morphological disparity in very different ways. Moreover, we show that when a mainland radiation derived from island ancestors comes into contact with an incumbent mainland radiation the ensuing interactions favor the island-derived clade.

Mechanisms of cancer metastasis.

Metastatic cancer is almost always terminal, and more than 90% of cancer deaths result from metastatic disease. Combating cancer metastasis and post-therapeutic recurrence successfully requires understanding each step of metastatic progression. This review describes the current state of knowledge of the etiology and mechanism of cancer progression from primary tumor growth to the formation of new tumors in other parts of the body. Open questions, avenues for future research, and therapeutic approaches with the potential to prevent or inhibit metastasis through personalization to each patient's mutation and/or immune profile are also highlighted.

A FOXC2 inhibitor, MC-1-F2, as a therapeutic candidate for targeting EMT in castration-resistant prostate cancer.

Androgen deprivation therapy (ADT) is the major treatment option for advanced prostate cancer. However, prostate cancer can develop into androgen-independent castration-resistant prostate cancer (CRPC) which is resistant to ADT. An alternative treatment strategy for CRPC can be targeting the epithelial-mesenchymal transition (EMT). EMT is governed by a series of transcription factors of which forkhead box protein C2 (FOXC2) is a central mediator. Our previous research into the inhibition of FOXC2 in breast cancer cells lead to the discovery of MC-1-F2, the first direct inhibitor of FOXC2. In current study on CRPC, MC-1-F2 has shown a decrease in mesenchymal markers, inhibition of cancer stem cell (CSC) properties and decrease in invasive capabilities of CRPC cell lines. We have also demonstrated a synergistic effect between MC-1-F2 and docetaxel treatments, leading to a decrease in docetaxel dosage, suggesting the possible combination therapy of MC-1-F2 and docetaxel for the effective treatment of CRPC.

Characterization of excretory/secretory products of the Taenia crassiceps cysticercus involved in the induction of regulatory T cells in vivo.

The ability to modulate the host immune response has allowed some parasites to establish themselves in the tissues of an immunocompetent organism. While some parasite excretion/secretion products (ESPs) were recently reported to induce differentiation of regulatory T cells (Tregs), their identity is not known. This work is aimed to identify and characterize ESPs of Taenia crassiceps cysticerci linked with Treg induction in vivo. ESPs were obtained from cultures of T. crassiceps cysticerci and inoculated in mice, measuring Treg levels by flow cytometry. Proteins in ESPs were analyzed by electrophoresis; then, ESPs were classified as either differential or conserved. Differentially included proteins were MS-sequenced and functionally characterized. Only 4 of 10 ESPs induced Tregs. Proteins with catalytic activity and those involved in immunological processes predominated, supporting the idea that these molecules could play an important role in the induction of Tregs.

γδ T Cells Kill Plasmodium falciparum in a Granzyme- and Granulysin-Dependent Mechanism during the Late Blood Stage.

Plasmodium spp., the causative agent of malaria, have a complex life cycle. The exponential growth of the parasites during the blood stage is responsible for almost all malaria-associated morbidity and mortality. Therefore, tight immune control of the intraerythrocytic replication of the parasite is essential to prevent clinical malaria. Despite evidence that the particular lymphocyte subset of γδ T cells contributes to protective immunity during the blood stage in naive hosts, their precise inhibitory mechanisms remain unclear. Using human PBMCs, we confirmed in this study that γδ T cells specifically and massively expanded upon activation with Plasmodium falciparum culture supernatant. We also demonstrate that these activated cells gain cytolytic potential by upregulating cytotoxic effector proteins and IFN-γ. The killer cells bound to infected RBCs and killed intracellular P. falciparum via the transfer of the granzymes, which was mediated by granulysin in a stage-specific manner. Several vital plasmodial proteins were efficiently destroyed by granzyme B, suggesting proteolytic degradation of these proteins as essential in the lymphocyte-mediated death pathway. Overall, these data establish a granzyme- and granulysin-mediated innate immune mechanism exerted by γδ T cells to kill late-stage blood-residing P. falciparum.

Salmonella enterica serovar Enteritidis biofilm lifestyle induces lower pathogenicity and reduces inflammatory response in a murine model compared to planktonic bacteria.

Salmonellaenterica serovar Enteritidis (S. Enteritidis) is the most frequent serovar involved in human salmonellosis. It has been demonstrated that about 80% of infections are related to biofilm formation. There is scant information about the pathogenicity of S. Enteritidis and its relationship to biofilm production. In this regard, this study aimed to investigate the differential host response induced by S. Enteritidis biofilm and planktonic lifestyle. To this purpose, biofilm and planktonic bacteria were inoculated to BALB/c mice and epithelial cell culture. Survival studies revealed that biofilm is less virulent than planktonic cells. Reduced signs of intestinal inflammation and lower bacterial translocation were observed in animals inoculated with Salmonella biofilm compared to the planktonic group. Results showed that Salmonella biofilm was impaired for invasion of non-phagocytic cells and induces a lower inflammatory response in vivo and in vitro compared to that of planktonic bacteria. Taken together, the outcome of Salmonella-host interaction varies depending on the bacterial lifestyle.

The Effect of Chest Compression Location and Aortic Perfusion in a Traumatic Arrest Model.

BACKGROUND: Recent evidence demonstrates that closed chest compressions directly over the left ventricle (LV) in a traumatic cardiac arrest (TCA) model improve hemodynamics and return of spontaneous circulation (ROSC) when compared to traditional compressions. Selective aortic arch perfusion (SAAP) also improves hemodynamics and controls hemorrhage in TCA. We hypothesized that chest compressions located over the LV would result in improved hemodynamics and ROSC in a swine model of TCA using SAAP. MATERIALS AND METHODS: Transthoracic echo was used to mark the location of the aortic root (Traditional location) and the center of the LV on animals (n = 24), which were randomized to receive chest compressions in one of the two locations. After hemorrhage, ventricular fibrillation (VF) was induced to simulate TCA. After a period of 10 min of VF, basic life support (BLS) with mechanical CPR was initiated and performed for 10 min, followed by advanced life support (ALS) for an additional 10 min. SAAP balloons were inflated at min 6 of BLS. Hemodynamic variables were averaged over the final 2 min of the BLS and ALS periods. Survival was compared between this SAAP cohort and a control group without SAAP (No-SAAP) (n = 26). RESULTS: There was no significant difference in ROSC between the two SAAP groups (P = 0.67). There was no ROSC difference between SAAP and No-SAAP (P = 0.74). CONCLUSIONS: There was no difference in ROSC between LV and Traditional compressions when SAAP was used in this swine model of TCA. SAAP did not confer a survival benefit compared to historical controls.

Effect of the Abdominal Aortic and Junctional Tourniquet on chest compressions in a swine model of ventricular fibrillation.

INTRODUCTION: Mortality for out-of-hospital cardiac arrest is high when traditional chest compressions are used without adjuncts. The abdominal aortic and junctional tourniquet (AAJT) is a device with a wedge-shaped air bladder that occludes the aortic bifurcation, augmenting blood flow to the heart and brain. Previously, the addition of AAJT during chest compression led to an increase in rate of survival in a model of traumatic cardiac arrest. HYPOTHESIS: This study was designed to determine if application of the AAJT would lead to more effective chest compressions as measured by improved hemodynamic parameters and an increased rate of return of spontaneous circulation (ROSC). METHODS: Yorkshire swine (n = 6 per group) underwent general anesthesia and instrumentation. Ventricular fibrillation (Vfib) was electrically induced and animals were allocated into groups with or without the AAJT. The AAJT was inflated if selected after four minutes of compressions. Following a total of ten minutes of compressions, the animals entered into a ten-minute advanced cardiac life support phase. Hemodynamics and blood gas measurements were compared between groups. RESULTS: ROSC or cardioversion from Vfib was not achieved in either group. The AAJT group had improved hemodynamic parameters with significantly higher carotid diastolic pressure and higher blood flow in the carotid artery (p = 0.016 and 0.028 respectively). However, no significant differences were observed with coronary perfusion pressure or end tidal CO2. CONCLUSION: The AAJT did not confer a survival advantage during chest compressions, but hemodynamic improvements were observed while the AAJT was in place.

The Effect of Chest Compression Location and Occlusion of the Aorta in a Traumatic Arrest Model.

BACKGROUND: Recent evidence demonstrates that closed chest compressions directly over the left ventricle (LV) in a traumatic cardiac arrest (TCA) model improve hemodynamics and return of spontaneous circulation (ROSC) when compared with traditional compressions. Resuscitative endovascular balloon occlusion of the aorta (REBOA) also improves hemodynamics and controls hemorrhage in TCA. We hypothesized that chest compressions located over the LV would result in improved hemodynamics and ROSC in a swine model of TCA using REBOA. MATERIALS AND METHODS: Transthoracic echo was used to mark the location of the aortic root (traditional location) and the center of the LV on animals (n = 26), which were randomized to receive chest compressions in one of the two locations. After hemorrhage, ventricular fibrillation was induced to simulate TCA. After a period of 10 min of ventricular fibrillation, basic life support (BLS) with mechanical cardiopulmonary resuscitation was initiated and performed for 10 min followed by advanced life support for an additional 10 min. REBOA balloons were inflated at 6 min into BLS. Hemodynamic variables were averaged during the final 2 min of the BLS and advanced life support periods. Survival was compared between this REBOA cohort and a control group without REBOA (no-REBOA cohort) (n = 26). RESULTS: There was no significant difference in ROSC between the two REBOA groups (P = 0.24). Survival was higher with REBOA group versus no-REBOA group (P = 0.02). CONCLUSIONS: There was no difference in ROSC between LV and traditional compressions when REBOA was used in this swine model of TCA. REBOA conferred a survival benefit regardless of compression location.

High-sucrose diet potentiates hyperaldosteronism and renal injury induced by stress in young adult rats.

Analyze the effect of stress and high-sucrose diet on serum aldosterone levels and the morphometric characteristics of the kidney in young adult rats. Wistar male rats aged 21 days old weaned were randomly assigned into four groups: control (C), stressed (St), high-sucrose diet (S30), and chronic restraint stress plus a 30% sucrose diet (St + S30). Rats were fed with a standard chow and tap water ad libitum (C group) or 30% sucrose diluted in water (S30 group) during eight weeks. The St and St + S30 groups were subject to restraint stress (1-hour daily in a plastic cylinder, 5 days per week), four weeks before euthanasia. At 81 days old, all animals were killed and blood samples and kidneys were collected. Stressed rats had an increase in the serum aldosterone and renal triacylglycerol, a decrease in the area of the renal corpuscle, glomeruli, proximal tubules, and aquaporin 2 expressions with loss of glomeruli. For its part, the high-sucrose diet decreased the area of the renal corpuscle, glomeruli, and aquaporin 2 expressions in the cortex. The combination of stress and high- sucrose diet maintained similar effects on the kidney as the stress alone, although it induced an increase in the creatinine levels and renal glycogen. Our results showed that chronic stress induces hyperaldosteronism and kidney injury. The intake of a high-sucrose diet may potentiate the renal injury promoted by stress.

Cervical cancer cells produce TGF-ß1 through the CD73-adenosine pathway and maintain CD73 expression through the autocrine activity of TGF-ß1.

In cancer, the adenosinergic pathway participates in the generation of an immunosuppressive microenvironment and in the promotion of tumor growth through the generation of adenosine (Ado). The present study analyzed the participation of Ado, generated through the functional activity of the cervical cancer (CeCa) pathway in CeCa cells, to induce the expression and secretion of TGF-ß1, as well as the participation of this factor to maintain CD73 expression. Ado concentrations greater than 10 µM were necessary to induce an increase of over 50% in the production and expression of TGF-ß1 in CeCa tumor cells. Blockade of A2AR and A2BR with the specific antagonists, ZM241385 and MRS1754, respectively, strongly reversed the production of TGF-ß1. TGF-ß1 produced by CeCa cells was necessary to maintain CD73 expression because the addition of anti-TGF-ß neutralizing antibodies or the inhibition of TGF-ßRI strongly reversed the expression of CD73 in the CeCa cells. These results suggested a feedback loop in CeCa cells that favors immunosuppressive activity through the production of TGF-ß1 and Ado as well as the autocrine activity of TGF-ß1 and expression of CD73.

A Traumatic Pulseless Electrical Activity Model: Mortality Increases With Hypovolemia Time.

BACKGROUND: There currently are no well-defined animal models for traumatic pulseless electrical activity (PEA). Our objective was to develop a swine model of traumatic PEA that would be useful for laboratory research where mortality is an outcome of interest. In this pilot study, we hypothesized that animals that remained in PEA without intervention for a longer period would have increased mortality. MATERIALS AND METHODS: Sixteen Yorkshire swine were alternately allocated to either 5 or 10 min of traumatic PEA without intervention. After the nonintervention period, basic life support (BLS) with mechanical cardiopulmonary resuscitation was initiated and performed for 10 min followed by advanced life support (ALS) for an additional 10 min. Hemodynamic and laboratory values are reported for baseline, posthemorrhage, end of BLS, and end of ALS periods. RESULTS: Mortality in the 10-min PEA group (100%) was higher than the 5-min group (38%) (P = 0.03). Animals in the 5-min group had improved aortic diastolic blood pressure, coronary perfusion pressure, and end-tidal CO2 at the end of both the BLS (P = 0.02, 0.002, and 0.02, respectively) and ALS (P = 0.009, 0.005, and 0.008, respectively). The 10-min animals had increased hyperkalemia at the end of the BLS (P = 0.004) and ALS (P = 0.005) periods. All animals in the 10-min group developed ventricular fibrillation (VF) and 38% of the 5-min animals developed VF (P = 0.03). CONCLUSIONS: In our pilot study of traumatic PEA in a swine model, a shorter period of nonintervention resulted in increased survival, improved hemodynamics during resuscitation, decreased hyperkalemia, and less incidence of conversion to VF arrest.

A prospective, randomized trial of intravenous hydroxocobalamin versus noradrenaline or saline for treatment of lipopolysaccharide-induced hypotension in a swine model.

Early, non-clinical studies support the use of hydroxocobalamin to treat sepsis-induced hypotension, but there is no translational, large animal model. The objective of this study was to compare survival in a sepsis model where large swine had endotoxaemia induced with lipopolysaccharide (LPS) and were treated with intravenous hydroxocobalamin (HOC), noradrenaline (NA), or saline. Thirty swine (45-55 kg) were anaesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Hypotension, predefined as 50% of baseline, was induced with LPS. Animals then received HOC, NA, or saline and monitored for 3 hours. The main outcome was survival to the conclusion of the study. Using a power of 80% and an alpha of 0.05, 10 animals were used per group. Secondary outcomes included: mean arterial pressure (MAP), systemic vascular resistance (SVR) and cardiac output (CO) along with several markers of sepsis. No differences were detected between groups at baseline or after hypotension. The survival distributions of the three groups were significantly different with more HOC animals surviving (10/10) compared with NA (8/10) or Saline (5/10) (log-rank P < 0.03). MAP was found to be higher in both the HOC and NA groups and HOC achieved the highest SVR. In this large animal, translational study of an endotoxaemic model of sepsis, hydroxocobalamin improved survival when compared with saline.

[Proposed Pedestrian Crosswalk Safety Rating for Mexico CityProposta de um índice de segurança de travessia de pedestres para a Cidade do México]. / Propuesta de un índice de seguridad de cruces peatonales para la Ciudad de México.

OBJECTIVE: Propose a pedestrian crosswalk safety rating (PCSR) for primary roads in Mexico City in order to rate crosswalk safety at intersections with a traffic light and then compare the PCSR with traffic accidents so as to empirically determine any association between the quality of the crosswalk and the traffic accident rate. METHODS: Identify criteria for the rating system through a state-of-the art review; weight the criteria to create a rating system through multicriterion analysis; design a stratified random sample of crosswalks (n = 490); and evaluate the data set. RESULTS: Through the PCSR, 91.3% of the crosswalks evaluated in Mexico City were found not to offer the conditions required to protect pedestrian safety; the "access" macro-criterion received the worst scores. The modelling shows that mixed land use and the length of the crosswalk are the most important variables in predicting traffic accidents. CONCLUSIONS: The analysis was relatively successful in showing the relationship between some variables (criteria) of the PCSR and traffic accidents. In many cases, this shows theoretical coherence; in others, research questions are raised.

OBJETIVO: Propor um índice de segurança de travessia de pedestres (ISTP) para as principais vias públicas na Cidade do México para classificar as travessias de pedestres semaforizadas e comparar o ISTP com os dados de trânsito para comprovar empiricamente se existe associação entre a qualidade dos locais de travessia e a taxa de acidentes. MÉTODOS: Foram identificados os critérios do índice com uma revisão do conhecimento atual e os critérios para gerar o ISTP foram ponderados com uso do método de análise de decisão multicritério e delineamento e avaliação de uma amostra aleatória estratificada de travessias de pedestres (n = 490). RESULTADOS: Com respeito à avaliação das travessias com o uso do ISTP, verificou-se que 91,3% das travessias avaliadas na Cidade do México não têm condições ideais para resguardar a segurança dos pedestres, com o macrocritério "acessibilidade" com a pior qualificação. Quanto à modelagem, observou-se que a mescla de usos do solo e a distância da travessia são as variáveis explicativas mais importantes para predizer a ocorrência de acidentes de trânsito. CONCLUSÕES: A análise demonstrou com relativo sucesso a relação entre algumas variáveis (critérios) que compõem o ISTP e acidentes de trânsito. Houve uma coerência teórica em muitos casos, porém em outros suscitou dúvidas a serem investigadas.

A Forkhead Box Protein†C2 Inhibitor: Targeting Epithelial-Mesenchymal Transition and Cancer Metastasis.

The epithelial-mesenchymal transition (EMT) has been suggested as a new target for therapeutic intervention of metastatic cancer. Forkhead box protein C2 (FOXC2) is known to be necessary for initiating and maintaining EMT, and therefore bestows on cancer cells metastatic and cancer stem cell (CSC)-like phenotypes, allowing cells to acquire higher motility, invasiveness, self-renewal, and therapy resistance. Here, we describe the first inhibitor of FOXC2, MC-1-F2. MC-1-F2 was able to induce cadherin switching and reverse EMT through the degradation of FOXC2 and blocking of its nuclear localization. In addition, MC-1-F2 was very effective in inhibiting cancer cell migration and invasion. As the first small-molecule inhibitor of FOXC2 and the first compound targeting EMT-associated transcription factor, MC-1-F2 will pave the way for a new anticancer therapeutic agent targeting metastatic cancer and help to elucidate the network of EMT signaling pathways.

When did anoles diverge? An analysis of multiple dating strategies.

Whereas most of the studies that discuss the evolutionary divergence of Anolis lizards have dated the clade's crown group in between 31 and 64 Ma, a single study has recovered a significantly older age for the same node (87 Ma). These differences also entail notable consequences on the preferred biogeographical hypothesis for the whole clade. Here we analyze a total of seven dating strategies by combining three calibration sources in independent BEAST runs to infer the most probable divergence timing for anole lizards (a mitochondrial rate for ND2 gene, the Anolis dominicanus fossil, and a group of fossils assigned to the Priscagamines, Iguanines, and Idontosaurus clades). Based on the estimated timing, we also addressed whether chronograms differ the most in deeper or shallower nodes by exploring the trend in the standard deviation of mean ages between chronograms across time. Next, we focus on the pattern for a single shallow node by hypothesizing the biogeography of the island-endemic Malpelo anole (Anolis agassizi), and evaluating the temporal congruence between the species' divergence and the island geology. The estimated set of ages suggests that anoles most likely diverged 72 Ma (71-73 Ma), with the crown group established around 58 Ma (51-65 Ma). Dispersal is therefore supported as the major driver in the biogeography of the group (and in Caribbean lineages in particular). Our analyses also indicated that (1) rate-based analyses pulled dates toward younger ages, (2) the differences in node ages between chronograms decrease towards the tips regardless of the position of the constrained node, and that (3) the estimated age for deep nodes (e.g. Anolis stem) is highly influenced when deep nodes are also constrained. The latter two results imply that the estimated age for shallower nodes is largely unaffected by the used temporal constraint. The congruence of all chronograms for the Malpelo anole also supports this finding. Anolis agassizi was found to have diverged before the emergence of Malpelo island in each analysis (anole: 19-31 Ma vs. Malpelo island: 16-17 Ma). Finally, we recommend when performing absolute dating analyses to first test for sequence saturation in the analyzed dataset (especially when calibrations are based on molecular rates). Our study also points out the importance of using multiple node constraints, especially when placed deeply in the tree, for fossil-based divergence dating analyses.

Amber fossils demonstrate deep-time stability of Caribbean lizard communities.

Whether the structure of ecological communities can exhibit stability over macroevolutionary timescales has long been debated. The similarity of independently evolved Anolis lizard communities on environmentally similar Greater Antillean islands supports the notion that community evolution is deterministic. However, a dearth of Caribbean Anolis fossils--only three have been described to date--has precluded direct investigation of the stability of anole communities through time. Here we report on an additional 17 fossil anoles in Dominican amber dating to 15-20 My before the present. Using data collected primarily by X-ray microcomputed tomography (X-ray micro-CT), we demonstrate that the main elements of Hispaniolan anole ecomorphological diversity were in place in the Miocene. Phylogenetic analysis yields results consistent with the hypothesis that the ecomorphs that evolved in the Miocene are members of the same ecomorph clades extant today. The primary axes of ecomorphological diversity in the Hispaniolan anole fauna appear to have changed little between the Miocene and the present, providing evidence for the stability of ecological communities over macroevolutionary timescales.

Left Ventricular Compressions Improve Hemodynamics in a Swine Model of Out-of-Hospital Cardiac Arrest.

INTRODUCTION: We hypothesized that chest compressions located directly over the left ventricle (LV) would improve hemodynamics, including coronary perfusion pressure (CPP), and return of spontaneous circulation (ROSC) in a swine model of cardiac arrest. METHODS: Transthoracic echocardiography (echo) was used to mark the location of the aortic root and the center of the left ventricle on animals (n = 26) which were randomized to receive chest compressions in one of the two locations. After a period of ten minutes of ventricular fibrillation, basic life support (BLS) with mechanical cardiopulmonary resuscitation (CPR) was initiated and performed for ten minutes followed by advanced cardiac life support (ACLS) for an additional ten minutes. During BLS the area of maximal compression was verified using transesophageal echo. CPP and other hemodynamic variables were averaged every two minutes. RESULTS: Mean CPP was not significantly higher in the LV group during all time intervals of resuscitation; mean CPP was significantly higher in the LV group during the 12-14 minute interval of BLS and during minutes 22-30 of ACLS (p < 0.05). Aortic systolic and diastolic pressures, right atrial systolic pressures, and end-tidal CO2 (ETCO2) were higher in the LV group during all time intervals of resuscitation (p < 0.05). Nine of the left ventricle group (69%) achieved ROSC and survived to 60 minutes compared to zero of the aortic root group (p < 0.001). CONCLUSIONS: In our swine model of cardiac arrest, chest compressions over the left ventricle improved hemodynamics and resulted in a greater proportion of animals with ROSC and survival to 60 minutes.

Comparative tests of the role of dewlap size in Anolis lizard speciation.

Phenotypic traits may be linked to speciation in two distinct ways: character values may influence the rate of speciation or diversification in the trait may be associated with speciation events. Traits involved in signal transmission, such as the dewlap of Anolis lizards, are often involved in the speciation process. The dewlap is an important visual signal with roles in species recognition and sexual selection, and dewlaps vary among species in relative size as well as colour and pattern. We compile a dataset of relative dewlap size digitized from photographs of 184 anole species from across the genus' geographical range. We use phylogenetic comparative methods to test two hypotheses: that larger dewlaps are associated with higher speciation rates, and that relative dewlap area diversifies according to a speciational model of evolution. We find no evidence of trait-dependent speciation, indicating that larger signals do not enhance any role the dewlap has in promoting speciation. Instead, we find a signal of mixed speciational and gradual trait evolution, with a particularly strong signal of speciational change in the dewlaps of mainland lineages. This indicates that dewlap size diversifies in association with the speciation process, suggesting that divergent selection may play a role in the macroevolution of this signalling trait.