Host–Pathogen Coevolution: The Selective Advantage of Bacillus thuringiensis Virulence and Its Cry Toxin Genes

Reciprocal coevolution between host and pathogen is widely seen as a major driver of evolution and biological innovation. Yet, to date, the underlying genetic mechanisms and associated trait functions that are unique to rapid coevolutionary change are generally unknown. We here combined experimental evolution of the bacterial biocontrol agent Bacillus thuringiensis and its nematode host Caenorhabditis elegans with large-scale phenotyping, whole genome analysis, and functional genetics to demonstrate the selective benefit of pathogen virulence and the underlying toxin genes during the adaptation process. We show that: (i) high virulence was specifically favoured during pathogen–host coevolution rather than pathogen one-sided adaptation to a nonchanging host or to an environment without host; (ii) the pathogen genotype BT-679 with known nematocidal toxin genes and high virulence specifically swept to fixation in all of the independent replicate populations under coevolution but only some under one-sided adaptation; (iii) high virulence in the BT-679-dominated populations correlated with elevated copy numbers of the plasmid containing the nematocidal toxin genes; (iv) loss of virulence in a toxin-plasmid lacking BT-679 isolate was reconstituted by genetic reintroduction or external addition of the toxins. We conclude that sustained coevolution is distinct from unidirectional selection in shaping the pathogen''s genome and life history characteristics. To our knowledge, this study is the first to characterize the pathogen genes involved in coevolutionary adaptation in an animal host–pathogen interaction system.     

Impact of GDP,Spending on R&D,Number of Universities and Scientific Journals on Research Publications among Asian Countries

Objectives

This study aimed to compare the impact of Gross Domestic Product (GDP) per capita, spending on Research and Development (R&D), number of universities, and Indexed Scientific Journals on total number of research documents (papers), citations per document and Hirsch index (H-index) in various science and social science subjects among Asian countries.

Materials and Methods

In this study, 40 Asian countries were included. The information regarding Asian countries, their GDP per capita, spending on R&D, total number of universities and indexed scientific journals were collected. We recorded the bibliometric indicators, including total number of research documents, citations per document and H-index in various science and social sciences subjects during the period 1996–2011. The main sources for information were World Bank, SCI-mago/Scopus and Web of Science; Thomson Reuters.

Results

The mean per capita GDP for all the Asian countries is 14448.31±2854.40 US$, yearly per capita spending on R&D 0.64±0.16 US$, number of universities 72.37±18.32 and mean number of ISI indexed journal per country is 17.97±7.35. The mean of research documents published in various science and social science subjects among all the Asian countries during the period 1996–2011 is 158086.92±69204.09; citations per document 8.67±0.48; and H-index 122.8±19.21. Spending on R&D, number of universities and indexed journals have a positive correlation with number of published documents, citations per document and H-index in various science and social science subjects. However, there was no association between the per capita GDP and research outcomes.

Conclusion

The Asian countries who spend more on R&D have a large number of universities and scientific indexed journals produced more in research outcomes including total number of research publication, citations per documents and H-index in various science and social science subjects.     

Phosphomimetic substitution of heterogeneous nuclear ribonucleoprotein A1 at serine 199 abolishes AKT-dependent internal ribosome entry site-transacting factor (ITAF) function via effects on strand annealing and results in mammalian target of rapamycin complex 1 (mTORC1) inhibitor sensitivity

The relative activity of the AKT kinase has been demonstrated to be a major determinant of sensitivity of tumor cells to mammalian target of rapamycin (mTOR) complex 1 inhibitors. Our previous studies have shown that the multifunctional RNA-binding protein heterogeneous nuclear ribonucleoprotein (hnRNP) A1 regulates a salvage pathway facilitating internal ribosome entry site (IRES)-dependent mRNA translation of critical cellular determinants in an AKT-dependent manner following mTOR inhibitor exposure. This pathway functions by stimulating IRES-dependent translation in cells with relatively quiescent AKT, resulting in resistance to rapamycin. However, the pathway is repressed in cells with elevated AKT activity, rendering them sensitive to rapamycin-induced G(1) arrest as a result of the inhibition of global eIF-4E-mediated translation. AKT phosphorylation of hnRNP A1 at serine 199 has been demonstrated to inhibit IRES-mediated translation initiation. Here we describe a phosphomimetic mutant of hnRNP A1 (S199E) that is capable of binding both the cyclin D1 and c-MYC IRES RNAs in vitro but lacks nucleic acid annealing activity, resulting in inhibition of IRES function in dicistronic mRNA reporter assays. Utilizing cells in which AKT is conditionally active, we demonstrate that overexpression of this mutant renders quiescent AKT-containing cells sensitive to rapamycin in vitro and in xenografts. We also demonstrate that activated AKT is strongly correlated with elevated Ser(P)(199)-hnRNP A1 levels in a panel of 22 glioblastomas. These data demonstrate that the phosphorylation status of hnRNP A1 serine 199 regulates the AKT-dependent sensitivity of cells to rapamycin and functionally links IRES-transacting factor annealing activity to cellular responses to mTOR complex 1 inhibition.     

Novel links among peroxiredoxins,endothelial dysfunction,and severity of atherosclerosis in type 2 diabetic patients with peripheral atherosclerotic disease

Peroxiredoxins, a group of antioxidant protein enzymes (PRDX1 to 6), are reported as antiatherogenic factors in animals; however, human studies are lacking. The present work aims to provide baseline data regarding the phenotype of PRDX1, 2, 4, and 6 in diabetic patients with peripheral atherosclerosis disease (PAD) and their relation to endothelial dysfunction (ED) and disease severity. Plasma levels of PRDX1, 2, 4, and 6 and markers of endothelial dysfunction (ICAM-1 and VCAM-1) were measured using ELISA in 55 type 2 diabetic patients having PAD and 25 healthy subjects. Ankle–brachial index (ABI), body mass index (BMI), triglycerides (TG), total cholesterol, HbA1c, and insulin resistance (HOMA IR) were measured. PRDX1, 2, 4, and 6 levels were significantly higher in patients compared to controls (PRDX1 21.9 ± 5.71 vs 16.8 ± 3.9 ng/ml, P < 0.001, PRDX2 36.5 ± 14.83 vs 20.4 ± 8.61 ng/ml, P < 0.001, PRDX4 3,840 ± 1,440 vs 2,696 ± 1,972 pg/ml, P < 0.005, PRDX6 311 ± 110 vs 287.9 ± 114 pg/ml, P < 0.05). PRDX1 and PRDX4 correlated negatively with ABI (r = −0.273, P < 0.05 and r = −0.28, P < 0.05, respectively), while PRDX1 and PRDX2 correlated positively with HOMA/IR and TG (r = 0.276, P < 0.01 and r = 0.295, P < 0.01, respectively). ICAM-1 was associated with PRDX2 and log PRDX6 (r = 0.345, P = 0.0037 and r = 0.344, P = 0.0038). Our results provide strong links among PRDXs, ED, and severity of PAD in diabetic patients which warrants further evaluation to clarify whether high circulating levels of PRDXs are a consequence of chronic atherosclerotic disease or a predisposing factor for later cardiovascular events.     

Progress in aromatase research and identification of key future directions

The IX International Aromatase Conference focused upon key developments in research related to the aromatase enzyme that had occurred since the last meeting. A session took place at the conclusion of conference discussing key areas for future research and issues currently facing researchers in the field. While significant progress on understanding structural elements of the enzyme and regulatory mechanisms of both the gene and protein provides an excellent basis for development of improved aromatase inhibitors and exploration of the important problem of aromatase inhibitor resistance, significant challenges remain. Increasing the speed with which findings are translated into clinical practice and finding an appropriate balance between basic and translational research were identified as areas which require further attention before the next meeting in 2010.     

Cement flow during impaction allografting: a finite element analysis

Cement intrusion into cancellous or impacted bone is not well understood. We adopted an engineering mechanics approach to predict the effect of surgical variables on the cement intrusion into impacted cancellous bone, used for the revision of failed total hip replacement with the impaction allografting technique. Specifically, a three-dimensional finite element model was used to determine the effects of cement viscosity, the magnitude and duration of pressurization, and the distribution of the porosity along the femur on cement intrusion. The overall averaged mean intrusion depth difference between the finite element model prediction and the cadaveric measurements was 1.1mm. The depth of penetration increased with higher pressurization pressure, duration of pressurization, and earlier stem insertion (lower viscosity), but maintained a similar profile. The distribution of the porosity along the femur determined the intrusion profile. Cement viscosity, the applied pressure or the duration of the pressurization can be adjusted to limit the cement volume injected into the medullary canal and therefore prevent the cement from reaching the endosteal surface.     

A model-free feature-based bi-planar RSA method for kinematic analysis of total knee arthroplasty

Fluoroscopic imaging is commonly used for assessing relative motions of orthopaedic implants. One limiting factor to in vivo model-based roentgen stereophotogrammetric analysis of total knee arthroplasty is the need for 3D models of the implants.The 3D models of the implant components must be reverse-engineered, if not provided by the company, which makes this method impractical for a clinical study involving many types or sizes of implants. This study introduces a novel feature-based methodology that registers the features at the implant-bone or implant-cement interface of the components that have elementary shapes. These features include pegs with hemispherical heads, and straight, circular or curved edges located on flat faces of the box of the femoral component or the stem geometry of the tibial component. Software was developed to allow easy registration of these features through a graphical user interface. The accuracy and precision of registration for multiple flexion angles from 0 to 120 deg was determined with reference to registered poses of the implants through experiments on bone replica models and also on a cadaver specimen implanted with total knee prostheses. When compared to an equivalent bi-planar model-based registration, the results were comparable: The mean accuracy of this feature-based method was 1.45 deg and 1.03 mm (in comparison to 0.95 deg and 1.32 mm for the model-based approach), and the mean precision was 0.57 deg and 0.26 mm (in comparison to 0.42 deg and 0.44 mm for the model-based approach).The methodology and the developed software can easily accommodate different design of implants with various fixation features. This method can facilitate in vivo kinematic analysis of total knee arthroplasty by eliminating the need for 3D models of the implant components.     

Down syndrome in two siblings with 47,XY,+21 and 46,XY/46,XY,-21,+t(21q;21q)

Summary This is the first report in the literature of siblings affected with Down syndrome; one sibling had a nondisjunction of chromosome 21 and the other a (21q;21q) translocation.     

Xylella fastidiosa Does Not Occur in Lebanon

Xylella fastidiosa has been reported as responsible for a devastating disease on olive trees in Apulia region (south‐eastern Italy), characterized by a quick decline syndrome. In Lebanon, the pathogen was recently associated with leaf scorch symptoms on oleander, and reports on leaf scorch and dieback of olive trees branches by technicians and farmers have shown an increasing trend in the main agricultural areas. To assess the occurrence and distribution of the pathogen in Lebanon, samples of twigs from olive trees (82), olive seedlings (26), grapevine (30), oleander (32) and ornamentals imported from Italy (48) were analysed by isolation on four agarized media, serological techniques (ELISA and DTBIA) using Xylella fastidiosa‐specific antibodies and by PCR, using three specific sets of primers. Results unequivocally demonstrated that all the collected samples were free from the pathogen. As well, both detection protocols and attempts at isolating the pathogen on agarized media demonstrated that oleander samples gathered from American University campus in Beirut, where X. fastidiosa was previously reported, were not infected. Nevertheless, continuous monitoring and rigorous control measures of propagative materials are necessary to prevent the introduction of Xylella fastidiosa in Lebanon.