Variation in resource acquisition and use among host clones creates key epidemiological trade‐offs

Parasites can certainly harm host fitness. Given such virulence, hosts should evolve strategies to resist or tolerate infection. But what governs those strategies and the costs that they incur? This study illustrates how a fecundity‐susceptibility trade‐off among clonally reared genotypes of a zooplankton (Daphnia dentifera) infected by a fungal parasite (Metschnikowia) arises due to variation in resource acquisition and use by hosts. To make these connections, we used lab experiments and theoretical models that link feeding with susceptibility, energetics, and fecundity of hosts. These feeding‐based mechanisms also produced a fecundity‐survivorship trade‐off. Meanwhile, a parasite spore yield–fecundity trade‐off arose from variation in juvenile growth rate among host clones (another index of resource use), a result that was readily anticipated and explained by the models. Thus, several key epidemiological trade‐offs stem from variation in resource acquisition and use among clones. This connection should catalyze the creation of new theory that integrates resource‐ and gene‐based responses of hosts to disease.     

Molecular systematics and morphological character evolution of the Condamineeae (Rubiaceae)

? Premise of the study: The Condamineeae have in previous molecular studies been shown to be part of an early-divergent clade within the subfamily Ixoroideae, together with the tribes Calycophylleae, and Hippotideae, and genera of the former Cinchoneae and Rondeletieae. Generic relationships within this clade have, however, remained largely unresolved. ? Methods: In this study, the systematics of the Condamineeae was further examined by phylogenetic reconstruction of six cpDNA regions and one nrDNA region using parsimony and Bayesian Markov chain Monte Carlo inference. Morphological character evolution within the tribe was assessed by ancestral state reconstruction using likelihood optimization of characters onto Bayesian trees. ? Key results: Calycophylleae appears polyphyletic. "Hippotideae" is monophyletic but nested within the Condamineeae. The phylogenetic hypotheses presented support a resurrection of the genera Holtonia, Schizocalyx, and Semaphyllanthe. Furthermore, Bathysa is found to be polyphyletic, Tresanthera is found nested within Rustia, and the taxonomically disputed genus Dialypetalanthus is here shown to be sister to a Bothriospora-Wittmackanthus clade. Morphological ancestral state reconstructions indicate that protogyny have evolved at least two times within the tribe and that indehiscent fruits, loculicidal fruit dehiscence, and intrapetiolar stipules have evolved independently several times. The occurrence of calycophylls (leaf-like calyx lobes), poricidal anthers, and winged seeds also appear homoplastic within the tribe. ? Conclusions: A diagnosis and delimitation of the tribe Condamineeae is presented, with taxonomic proposals to synonymize Tresanthera and to transfer several species of Bathysa as well as Phitopis to a resurrected Schizocalyx.     

A study on the applicability of implantable microchip transponders for body temperature measurements in pigs

Background  

The applicability of an electronic monitoring system using microchip transponders for measurement of body temperatures was tested in 6-week-old conventional Danish weaners infected with classical swine fever virus (CSFV). Subcutaneous tissue temperatures obtained by the implantable transponders were compared with rectal temperatures, recorded by a conventional digital thermometer.     

Prevalence and risk factors of vertebral compression fractures in female SLE patients

Introduction

The present study objective was to evaluate the incidence of methotrexate (MTX)-specific liver lesions from the analysis of a liver biopsy of inflammatory arthritis patients with elevated liver enzymes.

Methods

A case-control study was performed with 1,571 arthritis patients on long-term low-dose MTX therapy. Results of liver biopsy were analyzed in 41 patients with elevated liver enzymes. The expression of autoimmune markers was also assessed. This population was compared with 41 disease control subjects obtained from the same database, also on MTX but without elevated liver enzymes, matched for age, sex and rheumatic disease.

Results

Compared with the disease controls, patients with liver biopsy showed lower disease duration and lower MTX exposure, weekly and cumulative doses, reflecting shorter treatment duration due to liver abnormalities. Liver biopsies showed 17 autoimmune hepatitis-like (AIH-like) lesions, 13 nonalcoholic steatohepatitis-like lesions, seven limited liver lesions, and two primary biliary cirrhoses. However, MTX-specific lesions with dystrophic nuclei in hepatocytes were seen in only two cases. Liver biopsy lesions were associated with autoimmune markers (P = 0.007); notably, AIH-like lesions were associated with rheumatoid arthritis and with the presence of the HLA-DR shared epitope.

Conclusions

MTX-specific liver lesions are rarely observed in arthritis patients under long-term MTX therapy and elevated liver enzymes.     

Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk

Polymorphisms in DNA repair genes may be associated with differences in DNA repair capacity, thereby influencing the individual susceptibility to smoking-related cancer. We investigated the association of 10 base-excision and nucleotide-excision repair gene polymorphisms (XRCC1 -77 T/C, Arg194Trp, Arg280His and Arg399Gln; APE1 Asp148Glu; OGG1 Ser326Cys; XPA -4 G/A; XPC PAT; XPD Asp312Asn and Lys751Gln) with lung cancer risk in Caucasians. Genotypes were determined by PCR-RFLP and PCR-single base extension assays in 110 lung cancer patients and 110 age- and sex-matched controls, and the results were analyzed using logistic regression adjusted for relevant covariates. A significant association between the APE1 Asp148Glu polymorphism and lung cancer risk was found, with adjusted odds ratios (OR) of 3.38 (p=0.001) for the Asp/Glu genotype and 2.39 (p=0.038) for the Glu/Glu genotype. Gene-smoking interaction analyses revealed a statistically significant interaction between cumulative cigarette smoking and the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms: these polymorphisms were significantly associated with lung cancer in nonsmokers and light smokers (<25 PY; OR=4.92, p=0.021 for XRCC1 399 Gln/Gln; OR=3.62, p=0.049 for XPD 751 Gln/Gln), but not in heavy smokers (> or =25 PY; OR=0.68, p=0.566 for XRCC1 399 Gln/Gln; OR=0.46, p=0.295 for XPD 751 Gln/Gln). Both the XRCC1 Arg194Trp and Arg280His as well as the OGG1 Ser326Cys heterozygous genotypes were associated with a significantly reduced risk for lung cancer (OR=0.32, p=0.024; OR=0.25, p=0.028; OR=0.51, p=0.033, respectively). No associations with lung cancer risk were found for the XRCC1 -77 T/C, the XPA -4 G/A and the XPC PAT polymorphisms. In conclusion, the APE1 Asp148Glu polymorphism is highly predictive for lung cancer, and cumulative cigarette smoking modifies the associations between the XRCC1 Arg399Gln and the XPD Lys751Gln polymorphisms and lung cancer risk.     

Stepwise reduction of functional spinal structures increase range of motion and change lordosis angle

Many investigators have performed studies on specific defect situations or determined the contribution on isolated structures. Investigating the contribution of functional structures requires obtaining the kinematic response directly on spinal segments. The purpose of this study was to quantify the function of anatomical components on lumbar segments for different loading magnitudes. Eight spinal segments (L4-5) with a median age of 52 years (ranging from 38 to 59 years) and a low degree of disc degeneration were utilized for the in vitro testing. Specimens were mounted in a custom-built spine tester and loaded with pure moments (1-10 N m) to move within three anatomical planes at a loading rate of 1.0 degrees /s. Anatomy was successively reduced by: ligaments, facet capsules, joints and nucleus. Data were evaluated for range of motion, neutral zone and lordosis angle. Transection of posterior ligaments predominantly increased specimen flexion for all bending moments applied. Supraspinous ligament also indicated to resist in extension slightly, whereas the facet capsules did not. Facet joints contributed to axial rotation, but not in lateral bending. The anterior longitudinal ligament was found to slightly resist in axial rotation, but strongly in extension. Nucleotomy caused largest increase of all movements. The unloaded posture of the specimens changed after ligament dissection, indicating ligament pretension. The region of lumbar spine is interesting for finite element (FE) simulation due to the high evidence of disc degeneration and injuries. This study may help to understand the function of specific anatomical structures and assists in FE model calibration. We suggest to start a calibration procedure for such models with the smallest functional structure (annulus) and to cumulatively add further structures.     

A syntactic model to design and verify synthetic genetic constructs derived from standard biological parts

MOTIVATION: The sequence of artificial genetic constructs is composed of multiple functional fragments, or genetic parts, involved in different molecular steps of gene expression mechanisms. Biologists have deciphered structural rules that the design of genetic constructs needs to follow in order to ensure a successful completion of the gene expression process, but these rules have not been formalized, making it challenging for non-specialists to benefit from the recent progress in gene synthesis. RESULTS: We show that context-free grammars (CFG) can formalize these design principles. This approach provides a path to organizing libraries of genetic parts according to their biological functions, which correspond to the syntactic categories of the CFG. It also provides a framework for the systematic design of new genetic constructs consistent with the design principles expressed in the CFG. Using parsing algorithms, this syntactic model enables the verification of existing constructs. We illustrate these possibilities by describing a CFG that generates the most common architectures of genetic constructs in Escherichia coli. AVAILABILITY: A web site allows readers to experiment with the algorithms presented in this article: www.genocad.org. SUPPLEMENTARY INFORMATION: Sequences and models are available at Bioinformatics online.     

Eating yourself sick: transmission of disease as a function of foraging ecology

Species interactions may profoundly influence disease outbreaks. However, disease ecology has only begun to integrate interactions between hosts and their food resources (foraging ecology) despite that hosts often encounter their parasites while feeding. A zooplankton–fungal system illustrated this central connection between foraging and transmission. Using experiments that varied food density for Daphnia hosts, density of fungal spores and body size of Daphnia , we produced mechanistic yet general models for disease transmission rate based on broadly applicable components of feeding biology. Best performing models could explain why prevalence of infection declined at high food density and rose sharply as host size increased (a pattern echoed in nature). In comparison, the classic mass-action model for transmission performed quite poorly. These foraging-based models should broadly apply to systems in which hosts encounter parasites while eating, and they will catalyse future integration of the roles of Daphnia as grazer and host.     

Engineering proteinase K using machine learning and synthetic genes

Background  

Altering a protein's function by changing its sequence allows natural proteins to be converted into useful molecular tools. Current protein engineering methods are limited by a lack of high throughput physical or computational tests that can accurately predict protein activity under conditions relevant to its final application. Here we describe a new synthetic biology approach to protein engineering that avoids these limitations by combining high throughput gene synthesis with machine learning-based design algorithms.