Expressing the joint moments of drop jumps and sidestep cutting in different reference frames – does it matter?

Joint moments help us understand joint loading and muscle function during movement. However, the interpretation depends on the choice of reference frame, but the different reference frames have not been compared in dynamic, high-impact sporting movements. We have compared the magnitude and the resulting ranking of hip and knee joint moments expressed in the laboratory coordinate system, the local system of the distal segment and projected or decomposed to the Joint Coordinate System (JCS) axes. Hip and knee joint moments of drop jumps and sidestep cutting in 70 elite female handball players were calculated based on recordings from an eight-camera 240 Hz system and two force platforms and expressed with the four methods. The greatest variations in magnitude between conditions were seen for drop jump hip internal rotation (range: 0.31–0.71 Nm/kg) and sidestep cutting knee flexion (2.87–3.39 Nm/kg) and hip internal rotation (0.87–2.36 Nm/kg) and knee internal rotation (0.10–0.40 Nm/kg) moments. The rank correlations were highest between conditions for flexion moments (0.88–1.00) and sidestep cutting abduction moments (0.71–0.98). The rank correlations ranged from 0.64 to 0.73 for drop jump knee abduction moments and between −0.17 and 0.67 for hip and knee internal rotation moments. Expression of joint moments in different reference systems affects the magnitude and ranking of athletes. This lack of consistency may complicate the comparison and combination of results. Projection to the JCS is the only method where joint moments correspond to muscle and ligament loading. More widespread adoption of this convention could facilitate comparison of studies and ease the interpretation of results.     

Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia

The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions (encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions (encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population.     

Energetic consequences of contrasting winter migratory strategies in a sympatric Arctic seabird duet

At the onset of winter, warm‐blooded animals inhabiting seasonal environments may remain resident and face poorer climatic conditions, or migrate towards more favourable habitats. While the origins and evolution of migratory choices have been extensively studied, their consequences on avian energy balance and winter survival are poorly understood, especially in species difficult to observe such as seabirds. Using miniaturized geolocators, time‐depth recorders and a mechanistic model, we investigated the migratory strategies, the activity levels and the energy expenditure of the closely‐related, sympatrically breeding Brünnich's guillemots Uria lomvia and common guillemots Uria aalge from Bjørnøya, Svalbard. The two guillemot species from this region present contrasting migratory strategies and wintering quarters: Brünnich's guillemots migrate across the North Atlantic to overwinter off southeast Greenland and Faroe Islands, while common guillemots remain resident in the Barents, the Norwegian and the White Seas. Results show that both species display a marked behavioural plasticity to respond to environmental constraint, notably modulating their foraging effort and diving behaviour. Nevertheless, we provide evidence that the migratory strategy adopted by guillemots can have important consequences for their energy balance. Overall energy expenditure estimated for the non‐breeding season is relatively similar between both species, suggesting that both southward migration and high‐arctic winter residency are energetically equivalent and suitable strategies. However, we also demonstrate that the migratory strategy adopted by Brünnich's guillemots allows them to have reduced daily energy expenditures during the challenging winter period. We therefore speculate that ‘resident’ common guillemots are more vulnerable than ‘migrating’ Brünnich's guillemots to harsh winter environmental conditions.     

The molecular evolution and structural organization of group I introns at position 1389 in nuclear small subunit rDNA of myxomycetes

The number of nuclear group I introns from myxomycetes is rapidly increasing in GenBank as more rDNA sequences from these organisms are being sequenced. They represent an interesting and complex group of intervening sequences because several introns are mobile (or inferred to be mobile) and many contain large and unusual insertions in peripheral loops. Here we describe related group I introns at position 1389 in the small subunit rDNA of representatives from the myxomycete family Didymiaceae. Phylogenetic analyses support a common origin and mainly vertical inheritance of the intron. All S1389 introns from the Didymiaceae belong to the IC1 subclass of nuclear group I introns. The central catalytic core region of about 100 nt appears divergent in sequence composition even though the introns reside in closely related species. Furthermore, unlike the majority of group I introns from myxomycetes the S1389 introns do not self-splice as naked RNA in vitro under standard conditions, consistent with a dependence on host factors for folding or activity. Finally, the myxomycete S1389 introns are exclusively found within the family Didymiaceae, which suggests that this group I intron was acquired after the split between the families Didymiaceae and Physaraceae.     

Transcriptional Profiling of Adult Neural Stem-Like Cells from the Human Brain

There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33–60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.     

Chemically enhanced phytoextraction of lead-contaminated soils

The effects of the combined application of soil fungicide (benomyl) and ethylenediaminetetraacetic acid (EDTA) on lead (Pb) phytoextraction by ryegrass (Lolium perenne) were examined. Twenty-five pots of Pb-contaminated soil (200 mg Pb kg(-1)) were seeded with ryegrass and randomly arranged into the following treatments: (1) Control, (2) benomyl, (3) EDTA, (4) benomyl and EDTA (B+E), and (5) benomyl followed by an application of EDTA 14 days later (B .. . E). Chemicals were applied when plants had reached maximum growth. Plants were analyzed for foliage Pb concentration using inductively coupled argon plasma (ICAP) spectrometry. The synergistic effects of the combined benomyl and EDTA application (treatments 4 and 5) were made evident by the significantly (p < 0.05) highest foliage Pb concentrations. However, the foliage dry biomass was significantly lowest for plants in treatments 4 and 5. The bioaccumulation factor (BF) and phytoextraction ratio (PR) were highest for plants in treatment 5 followed by plants in treatment 4.     

1.5 Mb deletion of chromosome 4p16.3 associated with postnatal growth delay,psychomotor impairment,epilepsy, impulsive behavior and asynchronous skeletal development

Several Wolf-Hirschhorn syndrome patients have been studied, mouse models for a few candidate genes have been constructed and two WHS critical regions have been postulated, but the molecular basis of the syndrome remains poorly understood.     

Cardiac-restricted expression of the carboxyl-terminal fragment of GRK3 Uncovers Distinct Functions of GRK3 in regulation of cardiac contractility and growth: GRK3 controls cardiac alpha1-adrenergic receptor responsiveness

G protein-coupled receptor kinase-2 and -3 (GRK2 and GRK3) in cardiac myocytes catalyze phosphorylation and desensitization of different G protein-coupled receptors through specificity controlled by their carboxyl-terminal pleckstrin homology domain. Although GRK2 has been extensively investigated, the function of cardiac GRK3 remains unknown. Thus, in this study cardiac function of GRK3 was investigated in transgenic (Tg) mice with cardiac-restricted expression of a competitive inhibitor of GRK3, i.e. the carboxyl-terminal plasma membrane targeting domain of GRK3 (GRK3ct). Cardiac myocytes from Tg-GRK3ct mice displayed significantly enhanced agonist-stimulated alpha(1)-adrenergic receptor-mediated activation of ERK1/2 versus cardiac myocytes from nontransgenic littermate control (NLC) mice consistent with inhibition of GRK3. Tg-GRK3ct mice did not display alterations of cardiac mass or left ventricular dimensions compared with NLC mice. Tail-cuff plethysmography of 3- and 9-month-old mice revealed elevated systolic blood pressure in Tg-GRK3ct mice versus control mice (3-month-old mice, 136.8 +/- 3.6 versus 118.3 +/- 4.7 mm Hg, p < 0.001), an observation confirmed by radiotelemetric recording of blood pressure of conscious, unrestrained mice. Simultaneous recording of left ventricular pressure and volume in vivo by miniaturized conductance micromanometry revealed increased systolic performance with significantly higher stroke volume and stroke work in Tg-GRK3ct mice than in NLC mice. This phenotype was corroborated in electrically paced ex vivo perfused working hearts. However, analysis of left ventricular function ex vivo as a function of increasing filling pressure disclosed significantly reduced (dP/dt)(min) and prolonged time constant of relaxation (tau) in Tg-GRK3ct hearts at elevated supraphysiological filling pressure compared with control hearts. Thus, inhibition of GRK3 apparently reduces tolerance to elevation of preload. In conclusion, inhibition of cardiac GRK3 causes hypertension because of hyperkinetic myocardium and increased cardiac output relying at least partially on cardiac myocyte alpha(1)-adrenergic receptor hyper-responsiveness. The reduced tolerance to elevation of preload may cause impaired ability to withstand pathophysiological mechanisms of heart failure.     

Glomerular abundance of complement proteins characterized by proteomic analysis of laser-captured microdissected glomeruli associates with progressive disease in IgA nephropathy

Background

The clinical course of IgA nephropathy (IgAN) is variable and complement activation may predict prognosis. The present study investigated whether glomerular abundance of complement proteins associates with progression to end-stage renal disease (ESRD) in patients for whom prognosis could not be predicted based on clinical variables.

Methods

Based on data from the Norwegian Kidney Biopsy Registry and the Norwegian Renal Registry, three groups were included: IgAN patients with (n = 9) or without (n = 16) progression to ESRD during 10 years, and controls (n = 15) with a normal kidney biopsy. IgAN patients had eGFR > 45 ml/min/1.73 m² and non-nephrotic proteinuria at time of biopsy. Using stored formalin-fixed paraffin embedded kidney biopsy tissue, about 100 glomerular cross sections were microdissected for each patient. Samples were analyzed by liquid chromatography–tandem mass spectrometry and relative abundances of complement proteins were compared between groups.

Results

Proteomic analyses quantified 2018 proteins, of which 28 proteins belong to the complement system. As compared to IgAN patients without progressive disease, glomeruli from patients with progressive IgAN had significantly higher abundance of components of the classical and the terminal complement pathways, and inhibitory factors such as Factor H and factor H related proteins. Abundance of complement proteins classified progressors from non-progressors with an area under ROC curve of 0.91 (p = 0.001). Clinical and morphological data were similar between the two patient groups and could not predict progressive IgAN.

Conclusions

In conclusion, higher glomerular abundance of complement proteins was associated with a progressive clinical course in IgAN and are candidate biomarkers to predict prognosis.