Elevated CO2 degassing rates prevented the return of Snowball Earth during the Phanerozoic

The Cryogenian period (~720–635 Ma) is marked by extensive Snowball Earth glaciations. These have previously been linked to CO₂ draw-down, but the severe cold climates of the Cryogenian have never been replicated during the Phanerozoic despite similar, and sometimes more dramatic changes to carbon sinks. Here we quantify the total CO₂ input rate, both by measuring the global length of subduction zones in plate tectonic reconstructions, and by sea-level inversion. Our results indicate that degassing rates were anomalously low during the Late Neoproterozoic, roughly doubled by the Early Phanerozoic, and remained comparatively high until the Cenozoic. Our carbon cycle modelling identifies the Cryogenian as a unique period during which low surface temperature was more easily achieved, and shows that the shift towards greater CO₂ input rates after the Cryogenian helped prevent severe glaciation during the Phanerozoic. Such a shift appears essential for the development of complex animal life

The stealth episome: suppression of gene expression on the excised genomic island PPHGI-1 from Pseudomonas syringae pv. phaseolicola

Pseudomonas syringae pv. phaseolicola is the causative agent of halo blight in the common bean, Phaseolus vulgaris. P. syringae pv. phaseolicola race 4 strain 1302A contains the avirulence gene avrPphB (syn. hopAR1), which resides on PPHGI-1, a 106 kb genomic island. Loss of PPHGI-1 from P. syringae pv. phaseolicola 1302A following exposure to the hypersensitive resistance response (HR) leads to the evolution of strains with altered virulence. Here we have used fluorescent protein reporter systems to gain insight into the mobility of PPHGI-1. Confocal imaging of dual-labelled P. syringae pv. phaseolicola 1302A strain, F532 (dsRFP in chromosome and eGFP in PPHGI-1), revealed loss of PPHGI-1::eGFP encoded fluorescence during plant infection and when grown in vitro on extracted leaf apoplastic fluids. Fluorescence-activated cell sorting (FACS) of fluorescent and non-fluorescent PPHGI-1::eGFP F532 populations showed that cells lost fluorescence not only when the GI was deleted, but also when it had excised and was present as a circular episome. In addition to reduced expression of eGFP, quantitative PCR on sub-populations separated by FACS showed that transcription of other genes on PPHGI-1 (avrPphB and xerC) was also greatly reduced in F532 cells harbouring the excised PPHGI-1::eGFP episome. Our results show how virulence determinants located on mobile pathogenicity islands may be hidden from detection by host surveillance systems through the suppression of gene expression in the episomal state

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Scaling relationships based on partition coefficients and body sizes have similarities and interactions

The LC50 of compounds with a similar biological effect, at a given exposure period, is frequently plotted log-log against the octanol-water partition coefficient and a straight line is fitted for interpolation purposes. This is also frequently done for physiological properties, such as the weight-specific respiration rate, as function of the body weight of individuals. This paper focuses on the remarkable observation that theoretical explanations for these relationships also have strong similarities. Both can be understood as result of the covariation of the values of parameters of models of a particular type for the underlying processes, while this covariation follows logically from the model structure. The one-compartment model for the uptake and elimination of compounds by organisms is basic to the BioConcentration Factor (BCF), or the partition coefficient; the standard Dynamic Energy Budget model is basic to the (ultimate) body size. The BCF is the ratio of the uptake and the elimination rates; the maximum body length is the ratio of the assimilation (i.e. uptake of resources) and the maintenance (i.e. use of resources) rates. This paper discusses some shortcomings of descriptive approaches and conceptual aspects of theoretical explanations. The strength of the theory is in the combination of why metabolic transformation depends both on the BCF and the body size. We illustrate the application of the theory with several data sets from the literature

Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study

Biomarkers are increasingly being used in the management of patients with chronic heart failure (HF). Galectin-3 is a recently developed biomarker associated with fibrosis and inflammation, and it may play a role in cardiac remodeling in HF. We determined its prognostic value in patients with chronic HF. Patients with chronic HF (New York Heart Association functional class III or IV) who participated in the Deventer-Alkmaar heart failure study were studied. Galectin-3 levels were determined at baseline using a novel optimized enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to determine the prognostic value of this biomarker. We studied 232 patients; their mean age was 71 +/- A 10 years, 72% were male, and 96% were in NYHA class III. During a follow-up period of 6.5 years, 98 patients died. Galectin-3 was a significant predictor of mortality risk after adjustment for age and sex, and severity of HF and renal dysfunction, as assessed by NT-proBNP and estimated glomerular filtration rate, respectively (hazard ratio per standard deviation 1.24, 95% CI 1.03-1.50, P = 0.026). Plasma galectin-3 is a novel prognostic marker in patients with chronic HF. Its prognostic value is independent of severity of HF, as assessed by NT-proBNP levels, and it may potentially be used in the management of such patients

Does the attention General Practitioners pay to their patients' mental health problems add to their workload? A cross sectional national survey

BACKGROUND: The extra workload induced by patients with mental health problems may sometimes cause GPs to be reluctant to become involved in mental health care. It is known that dealing with patients' mental health problems is more time consuming in specific situations such as in consultations. But it is unclear if GPs who are more often involved in patients' mental health problems, have a higher workload than other GPs. Therefore we investigated the following: Is the attention GPs pay to their patients' mental health problems related to their subjective and objective workload? METHODS: Secondary analyses were made using data from the Second Dutch National Survey of General Practice, a cross sectional study conducted in the Netherlands in 2000–2002. A nationally representative selection of 195 GPs from 104 general practices participated in this National Survey. Data from: 1) a GP questionnaire; 2) a detailed log of the GP's time use during a week and; 3) an electronic medical registration system, including all patients' contacts during a year, were used. Multiple regression analyses were conducted with the GP's workload as an outcome measure, and the GP's attention for mental health problems as a predictor. GP, patient, and practice characteristics were included in analyses as potential confounders. RESULTS: Results show that GPs with a broader perception of their role towards mental health care do not have more working hours or patient contacts than GPs with a more limited perception of their role. Neither are they more exhausted or dissatisfied with the available time. Also the number of patient contacts in which a psychological or social diagnosis is made is not related to the GP's objective or subjective workload. CONCLUSION: The GP's attention for a patient's mental health problems is not related to their workload. The GP's extra workload when dealing in a consultation with patients' mental health problems, as is demonstrated in earlier research, is not automatically translated into a higher overall workload. This study does not confirm GPs' complaints that mental health care is one of the components of their job that consumes a lot of their time and energy. Several explanations for these results are discussed

Family doctor-driven follow-up for adult childhood cancer survivors supported by a web-based survivor care plan

To facilitate family doctor-driven follow-up for adult childhood cancer survivors, we developed a survivor care plan (SCP) for adult survivors and their family doctors. The SCP was accessible for survivors and their family doctors on a secure website and as a printed booklet. It included data on diagnosis, treatment and potential risks as well as recommendations for follow-up. Childhood cancer survivors who were off-treatment >= 5 years, aged >= 18 years and not involved in a long-term follow-up program were eligible. They were advised to visit their family doctor. The endpoints were numbers of participants, adherence of family doctors to the guidelines and satisfaction ratings. The eligibility criteria were fulfilled by 108 survivors. Three family doctors and 15 survivors refused, 10 survivors were non-responders. Of the remaining 80 survivors, 73 survivors visited 72 family doctors. Sixty-nine (96%) family doctors returned data of whom 60 (83%) fully adhered to the recommended tests. The majority of survivors and family doctors were satisfied about the SCP. A (web-based) SCP for survivors and family doctors can serve as an effective communication vehicle to provide adequate shared care by the long-term follow-up clinic and family doctors

Tension, Free Space, and Cell Damage in a Microfluidic Wound Healing Assay

We use a novel, microfluidics-based technique to deconstruct the classical wound healing scratch assay, decoupling the contribution of free space and cell damage on the migratory dynamics of an epithelial sheet. This method utilizes multiple laminar flows to selectively cleave cells enzymatically, and allows us to present a 'damage free' denudation. We therefore isolate the influence of free space on the onset of sheet migration. First, we observe denudation directly to measure the retraction in the cell sheet that occurs after cell-cell contact is broken, providing direct and quantitative evidence of strong tension within the sheet. We further probe the mechanical integrity of the sheet without denudation, instead using laminar flows to selectively inactivate actomyosin contractility. In both cases, retraction is observed over many cell diameters. We then extend this method and complement the enzymatic denudation with analogies to wounding, including gradients in signals associated with cell damage, such as reactive oxygen species, suspected to play a role in the induction of movement after wounding. These chemical factors are evaluated in combination with the enzymatic cleavage of cells, and are assessed for their influence on the collective migration of a non-abrasively denuded epithelial sheet. We conclude that free space alone is sufficient to induce movement, but this movement is predominantly limited to the leading edge, leaving cells further from the edge less able to move towards the wound. Surprisingly, when coupled with a gradient in ROS to simulate the chemical effects of abrasion however, motility was not restored, but further inhibited.Massachusetts Institute of Technology. Presidential FellowshipNational Institutes of Health (U.S.). Biotechnology Training FellowshipSingapore-MIT Alliance for Research and TechnologyMassachusetts Institute of Biotechnology Training GrantMassachusetts Institute of Technology (Open-source Funding

Display of probability densities for data from a continuous distribution

Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201