Can transposable element copy number distribution parameters be estimated from natural populations of Drosophila melanogaster?

The copy frequency distribution of a transposable element family in a Drosophila melanogaster natural population is generally characterised by the values of the Charlesworths' model parameters α and β (Charlesworth & Charlesworth, 1983). The estimation of these parameters is made using the observed distribution of the occupied sites in a population sample. Several results have been interpreted as due either to the influence of stochastic factors or to deterministic factors (transposition, excision, selection…). The accuracy of this method was tested by estimations performed on samples from simulated populations. The results show that with the sample size usually used for natural population studies, the confidence intervals are too large to reasonably deduce either the element copy number distribution or the values of transposition and excision rate and selective coefficients.     

Crepidolithus cantabriensis nov. sp., a new calcareous nannofossil (Prymnesiophyceae) from the Lower Jurassic of northern Spain

A new calcareous nannofossil, Crepidolithus cantabriensis nov. sp., is described from the Lower Jurassic marls and marly limestones of the Cantabrian Range (Northern Spain). The new species is characterized by medium-sized, normal to narrowly elliptical coccoliths with open central-areas. In the light microscope, under crossed nicols and in distal view, it displays a characteristic bicyclic extinction pattern. Its inner rim edge shows maximum birefringence colours, which vary from white to yellow, whereas the faintly outer rim margin exhibits low birefringence, tending to grey, and they are separated by a dark and sigmoidal isogyre. C. cantabriensis nov. sp. seems closely related to Crepidolithus crassus on the basis of shared morphological characters. Both of them have a distal shield composed of around thirty sub-vertical, dextrally imbricating laths. The central-area width of C. cantabriensis nov. sp. is approximately half of the coccolith width, whilst it is reduced to one or two tiny lenticular slits in C. crassus. Nevertheless, the phyletic relationships between C. cantabriensis nov. sp. and Crepidolithus cavus are not clear, since they show different rim structures, and C. cavus has a delicate bar aligned along the minor axis of its central area. The first specimens of C. cantabriensis nov. sp. have been recognized within the Raricostatum AZ in the Tudanca section. This species seems to be more abundant in the Reinosa area, which occupied a more distal position with respect to the Iberian Massif during the studied time interval. It is hypothesized here that C. cantabriensis nov. sp. could have inhabited the lower-photic zone.     

Sensory Neurons Contacting the Cerebrospinal Fluid Require the Reissner Fiber to Detect Spinal Curvature In Vivo

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Range optimization for target and organs at risk in dynamic adaptive passive scattering proton beam therapy – A proof of concept

PurposeThe purpose of this study was to design and develop a new range optimization for target and organs at risk (OARs) in dynamic adaptive proton beam therapy (PBT).MethodsThe new range optimization for target and OARs (RO-TO) was optimized to maintain target dose coverage but not to increase the dose exposure of OARs, while the other procedure, range optimization for target (RO-T), only focused on target dose coverage. A retrospective analysis of a patient who received PBT for abdominal lymph node metastases was performed to show the effectiveness of our new approach. The original plan (OP), which had a total dose of 60 Gy (relative biological effectiveness; RBE), was generated using six treatment fields. Bone-based registration (BR) and tumor-based registration (TR) were performed on each pretreatment daily CT image dataset acquired once every four fractions, to align the isocenter.ResultsBoth range adaptive approaches achieved better coverage (D_95%) and homogeneity (D_5%−D_95%) than BR and TR only. However, RO-T showed the greatest increases in D_2cc and D_mean values of the small intestine and stomach and exceeded the limitations of dose exposure for those OARs. RO-TO showed comparable or superior dose sparing compared with the OP for all OARs.ConclusionsOur results suggest that BR and TR alone may reduce target dose coverage, and that RO-T may increase the dose exposure to the OARs. RO-TO may achieve the planned dose delivery to the target and OARs more efficiently than the OP. The technique requires testing on a large clinical dataset.     

Determination of G-protein levels,ADP-ribosylation by cholera and pertussis toxins and the regulation of adenylyl cyclase activity in liver plasma membranes from lean and genetically diabetic (db/db)

Liver plasma membranes prepared from genetically diabetic (db/db) mice expressed levels of G_i α-2, G_i α-3 and G-protein β-subunits that were reduced by some 75, 63 and 73% compared with levels seen in membranes from lean animals. In contrast, there were no significant differences in the expression of the 42 and 45 kDa forms of G_s α-subunits. Pertussis toxin-catalysed ADP-ribosylation of membranes from lean animals identified a single 41 kDa band whose labelling was reduced by some 86% in membranes from diabetic animals. Cholera toxin-catalysed ADP-ribosylation identified two forms of G_s α-subunits whose labelling was about 4-fold greater in membranes from diabetic animals compared with those from lean animals. Maximal stimulations of adenylyl cyclase activity by forskolin (100 μM), GTP (100 μM), p[NH]ppG (100 μM), NaF (10 mM) and glucagon (10 μM) were similar in membranes from lean and diabetic animals, whereas stimulation by isoprenaline (100 μM) was lower by about 22%. Lower concentrations (EC₅₀-60 nM) of p[NH]ppG were needed to activate adenylyl cyclase in membranes from diabetic animals compared to those from lean animals (EC₅₀-158 nM). As well as causing activation, p[NH]ppG was capable of eliciting a pertussis toxin-sensitive inhibitory effect upon forskolin-stimulated adenylyl cyclase activity in membranes from both lean and diabetic animals. However, maximal inhibition of adenylyl cyclase activity in membranes from diabetic animals was reduced to around 60% of that found using membranes from lean animals. Pertussis toxin-treatment in vivo enhanced maximal stimulation of adenylyl cyclase by glucagon, isoprenaline and p[NH]ppG through a process suggested to be mediated by the abolition of functional G_i activity. The lower levels of expression of G-protein β-subunits, in membranes from diabetic compared with lean animals, is suggested to perturb the equilibria between holomeric and dissociated G-protein subunits. We suggest that this may explain both the enhanced sensitivity of adenylyl cyclase to stimulation by p[NH]ppG in membranes from diabetic animals and the altered ability of pertussis and cholera toxins to catalyse the ADP-ribosylation of G-proteins in membranes from these two animals.