Phylogenetic and functional relationships in pastures and meadows from the North Adriatic Karst

Probably due to its phytogeographic position, the grasslands in the North Adriatic Karst are among the richest grasslands in the world and harbour the highest small-scale density of plant species found in terrestrial habitats. Different moisture and soil conditions determine distinct vegetation types, such as meadows, composed by mesophyllous plants and on mesic conditions, and semi-natural pastures, composed by sclerophyllous plants and on oligotrophic conditions. Even though plants in these two vegetation types differ in some of their attributes, their functional and phylogenetic relationships remain to be tested. We used a dataset comprising 180 species, in which 48 plots in the meadows and 52 plots in the pastures had been sampled, and tested the phylogenetic and functional relationships between the two vegetation types. The pastures contained more original species, but both the pastures and the meadows are expected to be important to increase biodiversity at landscape level. Different community assembly processes occurred in the two vegetation types, with limiting similarity leading to functional overdispersion in the meadows and environmental filtering leading to functional clustering in the pastures. Overall, traits were convergent, leading to a clustered phylogenetic structure in the meadows, probably due to pair-wise competition, and an overdispersed phylogenetic structure in the pastures, where species from different clades were filtered by the oligotrophic conditions. Transhumance may have contributed to the random pattern of trait diversity we found across the nodes of the phylogenetic tree.     

Mx is dispensable for interferon-mediated resistance of chicken cells against influenza A virus

The type I interferon (IFN) system plays an important role in antiviral defense against influenza A viruses (FLUAV), which are natural chicken pathogens. Studies of mice identified the Mx1 protein as a key effector molecule of the IFN-induced antiviral state against FLUAV. Chicken Mx genes are highly polymorphic, and recent studies suggested that an Asn/Ser polymorphism at amino acid position 631 determines the antiviral activity of the chicken Mx protein. By employing chicken embryo fibroblasts with defined Mx-631 polymorphisms and retroviral vectors for the expression of Mx isoforms in chicken cells and embryonated eggs, we show here that neither the 631Asn nor the 631Ser variant of chicken Mx was able to confer antiviral protection against several lowly and highly pathogenic FLUAV strains. Using a short interfering RNA (siRNA)-mediated knockdown approach, we noted that the antiviral effect of type I IFN in chicken cells was not dependent on Mx, suggesting that some other IFN-induced factors must contribute to the inhibition of FLUAV in chicken cells. Finally, we found that both isoforms of chicken Mx protein appear to lack GTPase activity, which might explain the observed lack of antiviral activity.     

Mice with human immune system components as in vivo models for infections with human pathogens

Many pathogens relevant to human disease do not infect other animal species. Therefore, animal models that reconstitute or harbor human tissues are explored as hosts for these. In this review, we will summarize recent advances to utilize mice with human immune system components, reconstituted from hematopoietic progenitor cells in vivo. Such mice can be used to study human pathogens that replicate in leukocytes. In addition to studying the replication of these pathogens, the reconstituted human immune system components can also be analyzed for initiating immune responses and control against these infections. Moreover, these new animal models of human infectious disease should replicate the reactivity of the human immune system to vaccine candidates and, especially, the adjuvants contained in them, more faithfully.     

Discovery and optimization of 2-phenyloxazole derivatives as diacylglycerol acyltransferase-1 inhibitors

In a discovery effort to find safe and effective DGAT-1 inhibitors, we have identified 2-phenyloxazole 4-carboxamide 1 as a conformationally constrained analog of a hydrazide hit, which was previously identified from high-throughput screening. Further optimization of this series has led to chemically more stable 2-phenyloxazole-based DGAT-1 inhibitor 25 with improved solubility, cell-based activity, and pharmacokinetic properties. Compound 25 also demonstrated in vivo efficacy in a diet-induced obesity (DIO) rat model.     

A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD

The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one-third of familial ALS cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases identified to date.     

Lotus japonicus symRK-14 uncouples the cortical and epidermal symbiotic program

SYMRK is a leucine-rich-repeat (LRR)-receptor kinase that mediates intracellular symbioses of legumes with rhizobia and arbuscular mycorrhizal fungi. It participates in signalling events that lead to epidermal calcium spiking, an early cellular response that is typically considered as central for intracellular accommodation and nodule organogenesis. Here, we describe the Lotus japonicus symRK-14 mutation that alters a conserved GDPC amino-acid sequence in the SYMRK extracellular domain. Normal infection of the epidermis by fungal or bacterial symbionts was aborted in symRK-14. Likewise, epidermal responses of symRK-14 to bacterial signalling, including calcium spiking, NIN gene expression and infection thread formation, were significantly reduced. In contrast, no major negative effects on the formation of nodule primordia and cortical infection were detected. Cumulatively, our data show that the symRK-14 mutation uncouples the epidermal and cortical symbiotic program, while indicating that the SYMRK extracellular domain participates in transduction of non-equivalent signalling events. The GDPC sequence was found to be highly conserved in LRR-receptor kinases in legumes and non-legumes, including the evolutionarily distant bryophytes. Conservation of the GDPC sequence in nearly one-fourth of LRR-receptor-like kinases in the genome of Arabidopsis thaliana suggests, however, that this sequence might also play an important non-symbiotic function in this plant.     

Characterization of the ribonuclease activity on the skin surface

The rapid degradation of ribonucleic acids (RNA) by ubiquitous ribonucleases limits the efficacy of new therapies based on RNA molecules. Therefore, our aim was to characterize the natural ribonuclease activities on the skin and in blood plasma i.e. at sites where many drugs in development are applied. On the skin surfaces of Homo sapiens and Mus musculus we observed dominant pyrimidine-specific ribonuclease activity. This activity is not prevented by a cap structure at the 5'-end of messenger RNA (mRNA) and is not primarily of a 5'- or 3'-exonuclease type. Moreover, the ribonuclease activity on the skin or in blood plasma is not inhibited by chemical modifications introduced at the 2'OH group of cytidine or uridine residues. It is, however, inhibited by the ribonuclease inhibitor RNasin^® although not by the ribonuclease inhibitor SUPERase· In?. The application of our findings in the field of medical science may result in an improved efficiency of RNA-based therapies that are currently in development.     

Severe obstetric brachial plexus palsies can be identified at one month of age

Objective

To establish whether severe obstetric brachial plexus palsy (OBPP) can be identified reliably at or before three months of age.

Methods

Severe OBPP was defined as neurotmesis or avulsion of spinal nerves C5 and C6 irrespective of additional C7-T1 lesions, assessed during surgery and confirmed by histopathological examination. We first prospectively studied a derivation group of 48 infants with OBPP with a minimal follow-up of two years. Ten dichotomous items concerning active clinical joint movement and needle electromyography of the deltoid, biceps and triceps muscles were gathered at one week, one month and three months of age. Predictors for a severe lesion were identified using a two-step forward logistic regression analysis. The results were validated in two independent cohorts of OBPP infants of 60 and 13 infants.

Results

Prediction of severe OBPP at one month of age was better than at one week and at three months. The presence of elbow extension, elbow flexion and of motor unit potentials in the biceps muscle correctly predicted whether lesions were mild or severe in 93.6% of infants in the derivation group (sensitivity 1.0, specificity 0.88), in 88.3% in the first validation group (sensitivity 0.97, specificity 0.76) and in 84.6% in the second group (sensitivity of 1.0, specificity 0.66).

Interpretation

Infants with OBPP with severe lesions can be identified at one month of age by testing elbow extension, elbow flexion and recording motor unit potentials (MUPs) in the biceps muscle. The decision rule implies that children without active elbow extension at one month should be referred to a specialized center, while children with active elbow extension as well as active flexion should not. When there is active elbow extension, but no active elbow flexion an EMG is needed; absence of MUPs in the biceps muscle is an indication for referral.     

The stimulatory Gα(s) protein is involved in olfactory signal transduction in Drosophila

Seven-transmembrane receptors typically mediate olfactory signal transduction by coupling to G-proteins. Although insect odorant receptors have seven transmembrane domains like G-protein coupled receptors, they have an inverted membrane topology, constituting a key difference between the olfactory systems of insects and other animals. While heteromeric insect ORs form ligand-activated non-selective cation channels in recombinant expression systems, the evidence for an involvement of cyclic nucleotides and G-proteins in odor reception is inconsistent. We addressed this question in vivo by analyzing the role of G-proteins in olfactory signaling using electrophysiological recordings. We found that Gα_s plays a crucial role for odorant induced signal transduction in OR83b expressing olfactory sensory neurons, but not in neurons expressing CO₂ responsive proteins GR21a/GR63a. Moreover, signaling of Drosophila ORs involved Gα_s also in a heterologous expression system. In agreement with these observations was the finding that elevated levels of cAMP result in increased firing rates, demonstrating the existence of a cAMP dependent excitatory signaling pathway in the sensory neurons. Together, we provide evidence that Gα_s plays a role in the OR mediated signaling cascade in Drosophila.     

Root elongation rate is correlated with the length of the bare root apex of maize and lupin roots despite contrasting responses of root growth to compact and dry soils

Background

We investigated interacting effects of matric potential and soil strength on root elongation of maize and lupin, and relations between root elongation rates and the length of bare (hairless) root apex.

Methods

Root elongation rates and the length of bare root apex were determined for maize and lupin seedlings in sandy loam soil of various matric potentials (?0.01 to ?1.6 MPa) and bulk densities (0.9 to 1.5 Mg m^?3).

Results

Root elongation rates slowed with both decreasing matric potential and increasing penetrometer resistance. Root elongation of maize slowed to 10 % of the unimpeded rate when penetrometer resistance increased to 2 MPa, whereas lupin elongated at about 40 % of the unimpeded rate. Maize root elongation rate was more sensitive to changes in matric potential in loosely packed soil (penetrometer resistances <1 MPa) than lupin. Despite these differing responses, root elongation rate of both species was linearly correlated with length of the bare root apex (r² 0.69 to 0.97).

Conclusion

Maize root elongation was more sensitive to changes in matric potential and mechanical impedance than lupin. Robust linear relationships between elongation rate and length of bare apex suggest good potential for estimating root elongation rates for excavated roots.