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Genetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation in the Intracellular Pathogen Response (IPR), an important antiviral pathway in the model organism Caenorhabditis elegans against Orsay virus (OrV). The IPR involves transcriptional activity of 80 genes including the pals-genes. We examine the genetic variation in the pals-family for traces of selection and explore the molecular and phenotypic effects of having distinct pals-gene alleles. Genetic analysis of 330 global C. elegans strains reveals that genetic diversity within the IPR-related pals-genes can be categorized in a few haplotypes worldwide. Importantly, two key IPR regulators, pals-22 and pals-25, are in a genomic region carrying signatures of balancing selection, suggesting that different evolutionary strategies exist in IPR regulation. We infected eleven C. elegans strains that represent three distinct pals-22 pals-25 haplotypes with Orsay virus to determine their susceptibility. For two of these strains, N2 and CB4856, the transcriptional response to infection was also measured. The results indicate that pals-22 pals-25 haplotype shapes the defense against OrV and host genetic variation can result in constitutive activation of IPR genes. Our work presents evidence for balancing genetic selection of immunity genes in C. elegans and provides a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations.

Introduction: The latent reservoir is the main barrier on the road to HIV cure, and clinical approaches towards eradication are often evaluated by their effect on proviral DNA. To ensure inclusiveness and representativeness in HIV cure studies, proviral DNA quantification assays that are able to detect all common circulating HIV clades are urgently needed. Here, three HIV DNA assays targeting three different genomic regions were evaluated for their sensitivity and subtype-tolerance using digital PCR. Methods: A subtype-B-specific assay targeting gag (GAG) and two assays targeting conserved sequences in ltr and pol (LTR and JO) were assessed for their sensitivity and subtype-tolerance in digital PCR (Bio-Rad QX200), using a panel of serially diluted subtype reference plasmids as well as a panel of clinical isolates. Both panels represent subtypes A, B, C, D, F, G and circulating recombinant forms (CRFs) AE and AG, which together are responsible for 94% of HIV infections worldwide. Results: HIV subtype was observed to greatly affect HIV DNA quantification results. Robust regression analysis of the serially diluted plasmid panel showed that the GAG assay was only able to linearly quantify subtype B, D and G isolates (4/13 reference plasmids, average [R.sup.2] = 0.99), whereas LTR and JO were able to quantify all tested isolates (13/13 reference plasmids, respective average [R.sup.2] = 0.99 and 0.98). In the clinical isolates panel, isolates were considered detectable if all replicates produced a positive result. The GAG assay could detect HIV DNA in four out of five subtype B and one out of two subtype D isolates, whereas the LTR and JO assays detected HIV DNA in all twenty-nine tested isolates. LTR and JO results were found to be equally precise but more precise than GAG. Conclusions: The results demonstrate the need for a careful validation of proviral reservoir quantification assays prior to investigations into non-B subtype reservoirs. The LTR and JO assays can sensitively and reliably quantify HIV DNA in a panel that represents the worldwide most prevalent subtypes and CRFs (A, B, C, D, AE, F, G and AG), justifying their application in future trials aimed at global HIV cure. Keywords: human immunodeficiency virus; subtypes; reservoir; cure; quantification; digital PCR, 1 | INTRODUCTION The HIV-1 pandemic is countered using antiretroviral drugs that intervene in several steps of the viral life cycle. Effective treatment drastically reduces and durably suppresses plasma HIV [...]

Context. A characteristic feature of young stellar objects is their variability, which is caused by a variety of different physical processes. High-resolution interferometric observations in the near- and mid-infrared wavelength ranges spanning multiple epochs allow the detailed study of these processes. Aims. We aim at investigating the expected variations of the interferometric observables connected to changes in the measured photometric fluxes of a typical variable accreting central young stellar object with a circumstellar disk. Methods. We calculated visibilities and closure phases as well as the photometric flux of brightness distributions obtained using 3D Monte Carlo radiative transfer simulations for a model of a circumstellar disk with an accreting central star. Results. Changes in the accretion luminosity of the central object, that is, an accreting pre-main-sequence star, can lead to significant variations in the visibility and closure phase of the star-disk system measured with instruments at the Very Large Telescope Interferometer (VLTI) that can be related to changes in the photometric flux. Taking into account additional effects due to baseline variation, interferometric observations can provide valuable contributions to the understanding of the underlying processes. Additionally, we provide the web application VLTI B-VAR that allows the impact of the hour angle on the visibility and closure phase for customized intensity maps to be estimated. [ABSTRACT FROM AUTHOR]

Orsay virus (OrV) is the first virus known to be able to complete a full infection cycle in the model nematode species Caenorhabditis elegans. OrV is transmitted horizontally and its infection is limited by antiviral RNA interference (RNAi). However, we have no insight into the kinetics of OrV replication in C. elegans. We developed an assay that infects worms in liquid, allowing precise monitoring of the infection. The assay revealed a dual role for the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it limits the progression of the initial infection at the step of recognition of dsRNA. Secondly, it provides an inherited protection against infection in the offspring. This establishes the heritable RNAi response as anti-viral mechanism during OrV infections in C. elegans. Our results further illustrate that the inheritance of the anti-viral response is important in controlling the infection in the canonical wild type Bristol N2. The OrV replication kinetics were established throughout the worm life-cycle, setting a standard for further quantitative assays with the OrV-C. elegans infection model.

Genetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation in the Intracellular Pathogen Response (IPR), an important antiviral pathway in the model organism Caenorhabditis elegans against Orsay virus (OrV). The IPR involves transcriptional activity of 80 genes including the pals- genes. We examine the genetic variation in the pals -family for traces of selection and explore the molecular and phenotypic effects of having distinct pals -gene alleles. Genetic analysis of 330 global C. elegans strains reveals that genetic diversity within the IPR-related pals -genes can be categorized in a few haplotypes worldwide. Importantly, two key IPR regulators, pals-22 and pals-25 , are in a genomic region carrying signatures of balancing selection, suggesting that different evolutionary strategies exist in IPR regulation. We infected eleven C. elegans strains that represent three distinct pals-22 pals-25 haplotypes with Orsay virus to determine their susceptibility. For two of these strains, N2 and CB4856, the transcriptional response to infection was also measured. The results indicate that pals-22 pals-25 haplotype shapes the defense against OrV and host genetic variation can result in constitutive activation of IPR genes. Our work presents evidence for balancing genetic selection of immunity genes in C. elegans and provides a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations. [ABSTRACT FROM AUTHOR]

Context. Optical and infrared spatially unresolved multi-epoch observations have revealed the variability of pre-main sequence stars and/or their environment. Moreover, structures in orbital motion around the central star, resulting from planet-disk interaction, are predicted to cause temporal variations in the brightness distributions of protoplanetary disks. Through repeated observations of pre-main sequence stars with the Very Large Telescope Interferometer (VLTI) over nearly two decades, the ESO Archive has become a treasure chest containing unprecedented high-resolution multi-epoch near- and mid-infrared observations of the potential planet-forming regions in protoplanetary disks. Aims. We aim to investigate whether the existing multi-epoch observations provide evidence for the variability of the brightness distributions of the innermost few astronomical units of protoplanetary disks and to quantify any variations detected. Methods. We present different approaches to search for evidence of temporal variations based on multi-epoch observations obtained with the VLTI instruments PIONIER, AMBER, and MIDI for 68 pre-main sequence stars. Results. For nine objects in our sample, multi-epoch data obtained using equal baselines are available that allow us to directly detect variations in the visibilities due to temporally variable brightness distributions. Significant variations of the near-infrared visibilities obtained in different epochs with PIONIER and/or AMBER for HD 50138, DX Cha, HD 142527, V856 Sco, HD 163296, and R CrA were found. HD 37806, TW Hya, and CPD-36 6759 show no significant variations. By estimating the impact of a small variation of the baseline on the measured squared visibilities, we are able to compare the data of another 12 pre-main sequence stars. Thereby, we find evidence for temporal variations of the brightness distribution of one additional object, AK Sco. Besides the two binaries DX Cha and AK Sco, HD 50138 and V856 Sco also show signs of variability caused by variations of asymmetric structures in the brightness distribution. [ABSTRACT FROM AUTHOR]

Lespedeza cuneata (poorman's lucerne; sericea lespedeza), a tannin-rich perennial legume, was offered as hay to dry Merino ewes in a confined feeding experiment to evaluate the effect on the level of gastrointestinal parasite infection in sheep. Medicago sativa (a low tannin containing perennial legume) was used as the control treatment. Parameters faecal egg count (FEC), FAMACHA© scores and rectal temperatures were used. FECs were substantially lower ( p = 0.05) in the Lespedeza group after 35 days, together with a trend of higher rectal temperatures, compared with the Medicago group. Although non-significant ( p > 0.05), the higher rectal temperatures suggested a lower level of anaemia in the sheep on the Lespedeza ration and therefore, a lower parasite-worm burden. However, FAMACHA© scores showed no significant ( p > 0.05) differences between treatments despite the differences in FEC that were recorded, indicating that host homeostasis was possibly mediated by improved nutrition as a result of the high protein content of both experimental diets. [ABSTRACT FROM AUTHOR]

Orsay virus (OrV) is the first virus known to be able to complete a full infection cycle in the model nematode species Caenorhabditis elegans. OrV is transmitted horizontally and its infection is limited by antiviral RNA interference (RNAi). However, we have no insight into the kinetics of OrV replication in C. elegans. We developed an assay that infects worms in liquid, allowing precise monitoring of the infection. The assay revealed a dual role for the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it limits the progression of the initial infection at the step of recognition of dsRNA. Secondly, it provides an inherited protection against infection in the offspring. This establishes the heritable RNAi response as anti-viral mechanism during OrV infections in C. elegans. Our results further illustrate that the inheritance of the anti-viral response is important in controlling the infection in the canonical wild type Bristol N2. The OrV replication kinetics were established throughout the worm life-cycle, setting a standard for further quantitative assays with the OrV-C. elegans infection model. [ABSTRACT FROM AUTHOR]

Organismal development is the most dynamic period of the life cycle, yet we have only a rough understanding of the dynamics of gene expression during adolescent transition. Here we show that adolescence in Caenorhabditis elegans is characterized by a spectacular expression shift of conserved and highly polymorphic genes. Using a high resolution time series we found that in adolescent worms over 10,000 genes changed their expression. These genes were clustered according to their expression patterns. One cluster involved in chromatin remodelling showed a brief up-regulation around 50 h post-hatch. At the same time a spectacular shift in expression was observed. Sequence comparisons for this cluster across many genotypes revealed diversifying selection. Strongly up-regulated genes showed signs of purifying selection in non-coding regions, indicating that adolescence-active genes are constrained on their regulatory properties. Our findings improve our understanding of adolescent transition and help to eliminate experimental artefacts due to incorrect developmental timing. [ABSTRACT FROM AUTHOR]

This article presents the numerical, finite difference, Hartree-Fock method as a source of reference values of total energies, multipole moments, static polarizabilities and hyperpolarizabilities (αzz, βzzz, γzzzz, Az,zz and Bzz,zz) for atoms and diatomic molecules. The finite field method is used to evaluate polarizabilities and hyperpolarizabilities as derivatives of the dipole and quadrupole moments with respect to the field. The finite difference calculations are compared with other numerical and finite basis set results. Since the finite difference Hartree-Fock method is capable of producing multipole moments with 10-12 significant figure accuracy the high quality of (hyper)polarizability values can be guaranteed. [ABSTRACT FROM AUTHOR]

A comparison is made of the accuracy with which the total electronic energy can be calculated by using the finite basis set approach (the algebraic approximation) and the finite difference method in calculations employing the Hartree-Fock model for the open shell ground (X[sup 2]Σ[sup +]) states of the fluorides BaF and YbF. The convergence of the calculations carried out within the algebraic approximation is monitored by employing systematically constructed basis sets of increasing size. The difference between the finite basis set and finite difference Hartree-Fock energies is 2.6 µE[sub h] for BaF and 2.8 µE[sub h] for YbF. Dipole moments determined within the algebraic approximation are also compared with the corresponding finite difference expectation values. [ABSTRACT FROM AUTHOR]

The local orbital energy function is used to assess the quality of approximate Hartree-Fock orbitals obtained by invoking the algebraic approximation and using a finite basis set expansion. Systematic sequences of distributed universal even-tempered basis sets of sphericalharmonic Gaussian-type functions are used to generate orbitals for which the corresponding total Hartree-Fock energy approaches the 1 μ E [sub h] level of accuracy. A pilot study of the behaviour of the local energy function is made for the hydrogenic atom described by a sequence of even-tempered Gaussian basis sets. The results of prototype calculations for the Hartree-Fock ground state of the BF molecule at its equilibrium geometry are presented. Sequences of calculations which use atom-centred basis sets are investigated as well as sequences which also include bond centred functions. The effects of the bond centred functions on the local orbital energy function are analysed. The local orbital energy function is seen as a measure of the quality of calculations carried out within the matrix Hartree-Fock approximation which can be employed in cases where the corresponding finite difference Hartree-Fock results are not available. [ABSTRACT FROM AUTHOR]

A comparison is made of the accuracy with which the total electronic energy can be calculated by using either the finite basis set approach (the algebraic approximation) or finite difference methods in calculations employing the restricted Hartree-Fock model for the open-shell ground (X[sup 2] Sigma+) states of the Group IIa fluorides BeF, MgF, CaF and SrF. The convergence of the calculations carried out within the algebraic approximation is monitored by employing systematically constructed basis sets of increasing size. By using two different grids, the accuracy of the finite difference calculations has been estimated to be of the order of 10-2 muE[sub h] . The average difference between the finite basis set and finite difference total Hartree-Fock energies is 2.75 muE[sub h] . Dipole moments determined within the algebraic approximation are also compared with the corresponding finite difference expectation values. [ABSTRACT FROM AUTHOR]

A comparison is made of the accuracy with which the total electronic energy can be calculated by using either the finite basis set approach (the algebraic approximation) or finite difference methods in calculations employing the Hartree-Fock model for the open shell ground (X 2zeta +) states of the 13-electron systems BeF, BO, CN and N+2. The convergence of the calculations carried out within the algebraic approximation is monitored by employing systematically constructed basis sets of increasing size. The accuracy of the finite difference calculations is assessed by employing two grids of different sizes, one of 32617 points and the other of 132385 points. The total Hartree-Fock energies supported by these two grids differ by less than 0.05mu Eh. The average difference between the finite basis set and finite difference Hartreeh Fock energies is 1.3mu Eh. Dipole moments determined within the algebraic approximation are compared with the corresponding finite difference expectation values for the neutral species. [ABSTRACT FROM AUTHOR]

A comparison is made of the finite basis set approach (the algebraic approximation) and finite difference methods in calculations using the Hartree-Fock model for the ground (X1Sigma+) states of the heaviest Group IIIb fluorides: indium fluoride and thallium fluoride molecules. The XF molecules, X = In, Tl, are considered as a prototype for systems containing increasingly heavy atoms and a number of electrons. New finite difference Hartree-Fock calculations for the GaF ground state improve upon earlier results. The convergence of the calculations carried out within the algebraic approximation is monitored by employing systematically constructed basis sets of increasing size. The dependence of the finite difference calculations on the numerical grid employed is discussed. For the InF molecule, the total Hartree-Fock energy obtained with a grid of 595 595 points lies 15 mu E below the finite basis set energy. For the ground h state of TlF the finite basis set energy lies about 61 mu E above the converged finite difference result obtained on a grid of 595 595 points. For the TlF molecule, the matrix element required to evaluate the electric dipole moment volume interaction for the elementary particles in the Tl nucleus is evaluated from the finite difference Hartree-Fock wavefunction. [ABSTRACT FROM AUTHOR]

The orbital amplitude difference function is used to assess the quality of Hartree-Fock orbitals obtained by invoking the algebraic approximation for the BF ground-state. Systematic sequences of even-tempered, spherical-harmonic Gaussian-type basis functions are used to generate orbitals for which the corresponding total Hartree-Fock energy approaches the 1 mu E level of accuracy. Exact orbitals are obtained from finite difference calculations using h a grid based on spheroidal coordinates. The finite basis set approximations for the orbital are discretized. The accuracy of the discretization is assessed. For each occupied orbital a discretized representation of the orbital amplitude difference function is generated and analysed. [ABSTRACT FROM AUTHOR]

The article presents a study that focuses on the development of oar-boat-rower system model for the optimization of rowing performance. It cites the establishment of the model with parameters from mechanics, hydrodynamics and biomechanics. It also indicates the use of the model in evaluating the performance sensitivity to the parameters.