Low-field magnetic resonance imaging study on carpal arthritis in systemic sclerosis - low-grade erosive arthritis of carpal bones is an unexpected and frequent disease manifestation

Introduction

The aim of the present study was to assess the prevalence and characteristics of subclinical arthritis of carpal and metacarpophalangeal joints in patients with systemic sclerosis (SSc).

Methods

Low-field (0.2 T) magnetic resonance imaging (MRI) was performed in consecutive patients with SSc attending our center between January 2010 and March 2011. Results were assessed in a standardized manner using the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) and standardized assessments of all hand joints. Patients with arthritis due to overlap syndromes were excluded.

Results

Of 38 inpatients and eight outpatients who were screened for inclusion, 30 patients participated in the study and 26 patients could be evaluated. Erosions, bone marrow edema, synovitis, and joint effusions were found in 87%, 37%, 68%, and 58%, respectively, and 24% of patients had additional tenovaginitis. Arthritis affected only a low number of joints per analyzed hand. All bones and joints could be affected, but synovitis and bone marrow edema occurred predominantly in the proximal row of carpal bones, most frequently affecting the lunate bone. The extent of inflammatory changes measured with the RAMRIS correlated significantly with the functional status assessed with the validated German functional score questionnaire Funktionsfragebogen Hannover.

Conclusion

Low-grade arthritic changes on low-field MRI are frequent in patients with pure SSc. The features of arthritis in SSc differ from rheumatoid arthritis. The distribution, the MRI pattern and the predilection for the lunate bone raise the hypothesis that arthritis in SSc may be caused not only by immunological inflammation but also by ischemic mechanisms.     

Behavioural Lateralization in Budgerigars Varies with the Task and the Individual

Handedness/footedness and side biases are a well-known phenomenon in many animals, including humans. However, these so-called biases have mostly been studied at the population level - individual biases have received less attention, especially with regard to consistency over different tasks. Here we investigate behavioral lateralization in 12 male Budgerigars, Melopsittacus undulatus, a social parrot inhabiting the Australian bushlands. We performed 5 types of experiments to investigate lateralization, in tasks that involved climbing onto a perch, or landing on perches arranged in various configurations. The birds displayed highly significant, individually varying biases. The bias displayed by any particular individual varied with the task, in strength as well as polarity. Analysis of the data revealed that the preferred foot used for climbing did not coincide with the foot that was used while landing. Thus, landing choices are probably not determined by foot bias. Furthermore, these individual preferences were overridden completely when a bird had to perform a task simultaneously with another bird.     

DNA Barcode Identification of Podocarpaceae—The Second Largest Conifer Family

We have generated matK, rbcL, and nrITS2 DNA barcodes for 320 specimens representing all 18 extant genera of the conifer family Podocarpaceae. The sample includes 145 of the 198 recognized species. Comparative analyses of sequence quality and species discrimination were conducted on the 159 individuals from which all three markers were recovered (representing 15 genera and 97 species). The vast majority of sequences were of high quality (B ₃₀ = 0.596–0.989). Even the lowest quality sequences exceeded the minimum requirements of the BARCODE data standard. In the few instances that low quality sequences were generated, the responsible mechanism could not be discerned. There were no statistically significant differences in the discriminatory power of markers or marker combinations (p = 0.05). The discriminatory power of the barcode markers individually and in combination is low (56.7% of species at maximum). In some instances, species discrimination failed in spite of ostensibly useful variation being present (genotypes were shared among species), but in many cases there was simply an absence of sequence variation. Barcode gaps (maximum intraspecific p–distance > minimum interspecific p–distance) were observed in 50.5% of species when all three markers were considered simultaneously. The presence of a barcode gap was not predictive of discrimination success (p = 0.02) and there was no statistically significant difference in the frequency of barcode gaps among markers (p = 0.05). In addition, there was no correlation between number of individuals sampled per species and the presence of a barcode gap (p = 0.27).     

A Hereditary Spastic Paraplegia Mouse Model Supports a Role of ZFYVE26/SPASTIZIN for the Endolysosomal System

Hereditary spastic paraplegias (HSPs) are characterized by progressive weakness and spasticity of the legs because of the degeneration of cortical motoneuron axons. SPG15 is a recessively inherited HSP variant caused by mutations in the ZFYVE26 gene and is additionally characterized by cerebellar ataxia, mental decline, and progressive thinning of the corpus callosum. ZFYVE26 encodes the FYVE domain-containing protein ZFYVE26/SPASTIZIN, which has been suggested to be associated with the newly discovered adaptor protein 5 (AP5) complex. We show that Zfyve26 is broadly expressed in neurons, associates with intracellular vesicles immunopositive for the early endosomal marker EEA1, and co-fractionates with a component of the AP5 complex. As the function of ZFYVE26 in neurons was largely unknown, we disrupted Zfyve26 in mice. Zfyve26 knockout mice do not show developmental defects but develop late-onset spastic paraplegia with cerebellar ataxia confirming that SPG15 is caused by ZFYVE26 deficiency. The morphological analysis reveals axon degeneration and progressive loss of both cortical motoneurons and Purkinje cells in the cerebellum. Importantly, neuron loss is preceded by accumulation of large intraneuronal deposits of membrane-surrounded material, which co-stains with the lysosomal marker Lamp1. A density gradient analysis of brain lysates shows an increase of Lamp1-positive membrane compartments with higher densities in Zfyve26 knockout mice. Increased levels of lysosomal enzymes in brains of aged knockout mice further support an alteration of the lysosomal compartment upon disruption of Zfyve26. We propose that SPG15 is caused by an endolysosomal membrane trafficking defect, which results in endolysosomal dysfunction. This appears to be particularly relevant in neurons with highly specialized neurites such as cortical motoneurons and Purkinje cells.     

Diffusion- and Perfusion-Weighted Imaging in Acute Lacunar Infarction: Is There a Mismatch?

Purpose

Characterization of lacunar infarction (LI) by use of multimodal MRI including diffusion- and perfusion-weighted imaging (DWI, PWI) is difficult because of the small lesion size. Only a few studies evaluated PWI in LI and the results are inconsistent.

Methods

In 16 LI patients who underwent initial MRI within 6 hours after symptom onset and follow-up MRI within 1 week demographics, clinical presentation, and MRI findings were analyzed with special emphasis on DWI and PWI findings. Time to peak maps were classified as showing a normal perfusion pattern or areas of hypoperfusion which were further categorized in mismatch (PWI>DWI), inverse mismatch (PWI<DWI), and match (PWI=DWI). Quantitative perfusion maps were generated and analyzed by use of Signal Processing in NMR-Software (SPIN).

Results

Of the 16 patients (mean age 65.5±12.9 years), 14 (87.5%) were male. Clinical symptoms comprised dysarthria (50%), hemiparesis (81.3%), and hemihypaesthesia (18.8%). Intravenous thrombolysis was performed in 7 (43.8%) patients. Clinical improvement was observed in 12 patients (75 %), while 2 (12.5%) patients showed a deterioration and another 2 (12.5%) a stable course. Acute ischemic lesions (mean volume of 0.46±0.29 cm³) were located in the thalamus (n=8, 50%), internal capsule (n=4, 25%), corona Radiata (n=3, 18.8%) and the mesencephalon (n=1, 6.3%). Circumscribed hypoperfusion (mean volume 0.61±0.48 cm³) was evident in 10 (62.5%) patients. Of these, 3 patients demonstrated a match, 4 an inverse mismatch, and 3 a mismatch between DWI and PWI lesion. Mean CBF and CBV ratios were 0.65±0.28 and 0.84±0.41 respectively. Growth of DWI lesions was observed in 7 (43.8%) and reversal of DWI lesions in 3 (18.8%) patients.

Conclusions

MRI allows identification of different DWI and PWI patterns in LI, including growth and reversal of ischemic lesions. Consequently, it may serve for a better characterization of this stroke subtype and support treatment decisions in daily clinical practice.     

Corynebacterium jeikeium jk0268 Constitutes for the 40 Amino Acid Long PorACj,Which Forms a Homooligomeric and Anion-Selective Cell Wall Channel

Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed.     

De novo indol-3-ylmethyl glucosinolate biosynthesis,and not long-distance transport,contributes to defence of Arabidopsis against powdery mildew

Powdery mildew is a fungal disease that affects a wide range of plants and reduces crop yield worldwide. As obligate biotrophs, powdery mildew fungi manipulate living host cells to suppress defence responses and to obtain nutrients. Members of the plant order Brassicales produce indole glucosinolates that effectively protect them from attack by non-adapted fungi. Indol-3-ylmethyl glucosinolate is constitutively produced in the phloem and transported to epidermal cells for storage. Upon attack, indol-3-ylmethyl glucosinolate is activated by CYP81F2 to provide broad-spectrum defence against fungi. How de novo biosynthesis and transport contribute to defence of powdery mildew-attacked epidermal cells is unknown. Bioassays and glucosinolate analysis demonstrate that GTR glucosinolate transporters are not involved in antifungal defence. Using quantitative live-cell imaging of fluorophore-tagged markers, we show that accumulation of the glucosinolate biosynthetic enzymes CYP83B1 and SUR1 is induced in epidermal cells attacked by the non-adapted barley powdery mildew Blumeria graminis f.sp. hordei. By contrast, glucosinolate biosynthesis is attenuated during interaction with the virulent powdery mildew Golovinomyces orontii. Interestingly, SUR1 induction is delayed during the Golovinomyces orontii interaction. We conclude that epidermal de novo synthesis of indol-3-ylmethyl glucosinolate contributes to CYP81F2-mediated broad-spectrum antifungal resistance and that adapted powdery mildews may target this process.     

A major locus controls a biologically active pheromone component in Heliconius melpomene

Understanding the production, response, and genetics of signals used in mate choice can inform our understanding of the evolution of both intraspecific mate choice and reproductive isolation. Sex pheromones are important for courtship and mate choice in many insects, but we know relatively little of their role in butterflies. The butterfly Heliconius melpomene uses a complex blend of wing androconial compounds during courtship. Electroantennography in H. melpomene and its close relative Heliconius cydno showed that responses to androconial extracts were not species specific. Females of both species responded equally strongly to extracts of both species, suggesting conservation of peripheral nervous system elements across the two species. Individual blend components provoked little to no response, with the exception of octadecanal, a major component of the H. melpomene blend. Supplementing octadecanal on the wings of octadecanal-rich H. melpomene males led to an increase in the time until mating, demonstrating the bioactivity of octadecanal in Heliconius. Using quantitative trait locus (QTL) mapping, we identified a single locus on chromosome 20 responsible for 41% of the parental species’ difference in octadecanal production. This QTL does not overlap with any of the major wing color or mate choice loci, nor does it overlap with known regions of elevated or reduced F_ST. A set of 16 candidate fatty acid biosynthesis genes lies underneath the QTL. Pheromones in Heliconius carry information relevant for mate choice and are under simple genetic control, suggesting they could be important during speciation.