Host preference of the facultative hyperparasitoidTetrastichus howardi (Hym.: Eulophidae)

Tetrastichus howardi (Olliff) preferred the lepidopteran hosts,Chilo partellus (Swinhoe) (Pyralidae) andHelicoverpa armigera (Hübner) (Noctuidae) to their parasitoids,Xanthopimpla stemmator (Thunberg) (Hymenoptera: Ichneumonidae) andPalexorista laxa (Curran) (Diptera: Tachinidae). IfT. howardi had previously experienced parasitising a certain host, its preference for that host increased, but not significantly. When reared on a certain host, the preference for that host increased.T. howardi showed no preference to any particular age of its hosts.T. howardi was able to discriminate between parasitised and unparasitised hosts, initially preferring parasitised hosts, but two days later preferring unparasitised hosts.     

Clinical Efficacy of Simulated Vitreoretinal Surgery to Prepare Surgeons for the Upcoming Intervention in the Operating Room

Purpose

To evaluate the efficacy of the virtual reality training simulator Eyesi to prepare surgeons for performing pars plana vitrectomies and its potential to predict the surgeons’ performance.

Methods

In a preparation phase, four participating vitreoretinal surgeons performed repeated simulator training with predefined tasks. If a surgeon was assigned to perform a vitrectomy for the management of complex retinal detachment after a surgical break of at least 60 hours it was randomly decided whether a warmup training on the simulator was required (n = 9) or not (n = 12). Performance at the simulator was measured using the built-in scoring metrics. The surgical performance was determined by two blinded observers who analyzed the video-recorded interventions. One of them repeated the analysis to check for intra-observer consistency. The surgical performance of the interventions with and without simulator training was compared. In addition, for the surgeries with simulator training, the simulator performance was compared to the performance in the operating room.

Results

Comparing each surgeon’s performance with and without warmup trainingshowed a significant effect of warmup training onto the final outcome in the operating room. For the surgeries that were preceeded by the warmup procedure, the performance at the simulator was compared with the operating room performance. We found that there is a significant relation. The governing factor of low scores in the simulator were iatrogenic retinal holes, bleedings and lens damage. Surgeons who caused minor damage in the simulation also performed well in the operating room.

Conclusions

Despite the large variation of conditions, the effect of a warmup training as well as a relation between the performance at the simulator and in the operating room was found with statistical significance. Simulator training is able to serve as a warmup to increase the average performance.     

Pleiotropic Functions of Tumor Suppressor WWOX in Normal and Cancer Cells

WW domain-containing oxidoreductase (WWOX), originally marked as a likely tumor suppressor gene, has over the years become recognized for its role in a much wider range of cellular activities. Phenotypic effects displayed in animal studies, along with resolution of WWOX''s architecture, fold, and binding partners, point to the protein''s multifaceted biological functions. Results from a series of complementary experiments seem to indicate WWOX''s involvement in metabolic regulation. More recently, clinical studies involving cases of severe encephalopathy suggest that WWOX also plays a part in controlling CNS development, further expanding our understanding of the breadth and complexity of WWOX behavior. Here we present a short overview of the various approaches taken to study this dynamic gene, emphasizing the most recent findings regarding WWOX''s metabolic- and CNS-associated functions and their underlying molecular basis.     

Trisubstituted pyrimidines as transient receptor potential vanilloid 1 (TRPV1) antagonists with improved solubility

A series of trisubstituted pyrimidines were synthesized to improve aqueous solubility of our first TRPV1 clinical candidate (1; AMG 517), while maintaining potent TRPV1 inhibitory activity. Structure-activity and structure-solubility studies led to the identification of compound 26. The aqueous solubility of 26 (>or=200microg/mL, 0.01 HCl; 6.7microg/mL, phosphate buffered saline (PBS); 150microg/mL, fasted-state simulated intestinal fluid (SIF)) was significantly improved over 1. In addition, compound 26 was found to be orally bioavailable (rat F(oral)=24%) and had potent TRPV1 antagonist activity (capsaicin IC(50)=1.5nM) comparable to that of 1.     

Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center

Molecular Biology Reports - Lung adenocarcinoma patients have variable prognosis due to many factors. Detection of epidermal growth factor receptor (EGFR) activating mutations is one of the factors...     

Brugia malayi: comparison of protective immune responses induced by Bm-alt-2 DNA, recombinant Bm-ALT-2 protein and prime-boost vaccine regimens in a jird model

Immunization of jirds with Bm-alt-2 elicited partial protection against challenge infection with the filarial parasite Brugia malayi. In this study, we initially compared the protective immune responses elicited following immunization with recombinant Bm-ALT-2 protein regimen and Bm-alt-2 DNA regimen. These studies showed that protein vaccination conferred approximately 75% protection compared to DNA vaccination that conferred only 57% protection. Analysis of the protective immune responses showed that the protein immunization promoted a Th2-biased response with an increase in IL-4, IL-5 and IgG1 responses, whereas, the DNA vaccine promoted a Th1-biased response with profound IFN-gamma and IgG2a responses. Since protein vaccination gave better results than DNA vaccination, we then wanted to evaluate whether a prime-boost vaccination that combined DNA prime and protein boost will significantly increase the protective responses induced by the protein vaccine. Our results suggest that prime-boost vaccination had no added advantage and was comparatively less effective (64% protection) than the Bm-ALT-2 protein alone vaccination. Prime boost vaccination generated mixed Th1/Th2 responses with a slightly diminished Th2 responses compared to protein vaccination. Thus, our results suggest that Bm-ALT-2 protein vaccination regimen may be slightly better than prime-boost vaccine regimen and the mechanism of protection appears to be largely mediated by a Th2-biased response.     

Predicting fracture of the femoral neck

A prediction of the probability of safe loading of the femoral neck, based on queueing theory, is presented. The following methods have been applied: (I) criterion of bone fracture was formulated, taking into consideration the complex state of stress-strain in the porosity zones of the bone; (II) tensile stresses around pores in the stretched zone of the bone were evaluated; (III) the influence of random events of the critical regimes of loading was modeled. The evaluation of the probability of safe loading of bones was obtained based on the levels of the tensile stresses, Young's moduli and ultimate tensile stresses which are affected by the increase in bone porosity and the distribution of the pores. Examples of analysis involving typical mechanical properties of bone in areas of vascular and lacunar-canalicular porosity are demonstrated. The ranges of initial average values of effective Young's moduli and ultimate tensile strengths were taken as 15.8-17.5GPa and 83-95MPa, respectively. The present analysis discovers the existence of three levels of safe loading: (1) a relatively safe level of the nominal tensile stresses (smaller than (2.8-3.2)MPa) where the probability of safe loading is of the order of 0.95 for the bone porosity which is less than 0.15; (2) an intermediate level of safety where the nominal tensile stresses are below (4.2-4.8)MPa and the probability of safe loading is 0.89 or higher, for the same level of bone porosity; (3) a critical level of safe loading where the nominal tensile stresses are about (8.3-9.5)MPa; they lead to sharp drop of probabilities of safe loading to 0.85-0.8 if the porosity is about 0.10 and to probabilities of 0.41-0.4 if the porosity is about 0.15.     

Quasi-steady-state kinetics at enzyme and substrate concentrations in excess of the Michaelis-Menten constant

In vitro enzyme reactions are traditionally conducted under conditions of pronounced substrate excess since this guarantees that the bound enzyme is at quasi-steady-state (QSS) with respect to the free substrate, thereby justifying the Briggs-Haldane approximation (BHA). In contrast, intracellular reactions, amplification assays, allergen digestion assays and industrial applications span a range of enzyme-to-substrate ratios for which the BHA is invalid, including the extreme of enzyme excess. The quasi-equilibrium approximation (QEA) is valid for a subset of enzyme excess states. Previously, we showed that the total QSSA (tQSSA) overlaps and extends the validity of the BHA and the QEA, and that it is at least roughly valid for any total substrate and enzyme concentrations. The analysis of the tQSSA is hampered by square root nonlinearity. Previous simplifications of the tQSSA rate law are valid in a parameter domain that overlaps the validity domains of the BHA and the QEA and only slightly extends them. We now integrate the tQSSA rate equation in closed form, without resorting to further approximations. Moreover, we introduce a complimentary simplification of the tQSSA rate law that is valid in states of enzyme excess when the absolute difference between total enzyme and substrate concentrations greatly exceeds the Michaelis-Menten constant. This includes a wide range of enzyme and substrate concentrations where both the BHA and the QEA are invalid and allows us to define precisely the conditions for zero-order and first-order product formation. Remarkably, analytical approximations provided by the tQSSA closely match the expected stochastic kinetics for as few as 15 reactant molecules, suggesting that the conditions for the validity of the tQSSA and for its various simplifications are also of relevance at low molecule numbers.