Sarcoid-derived fibroblasts: links between genomic instability, energy metabolism and senescence.

Bovine papillomavirus 1 (BPV-1) is a well recognized etiopathogenetic factor in a cancer-like state in horses, namely equine sarcoid disease. Nevertheless, little is known about BPV-1-mediated cell transforming effects. It was shown that BPV-1 triggers genomic instability through DNA hypomethylation and oxidative stress. In the present study, we further characterized BPV-1-positive fibroblasts derived from sarcoid tumors. The focus was on cancer-like features of sarcoid-derived fibroblasts, including cell cycle perturbation, comprehensive DNA damage analysis, end-replication problem, energy metabolism and oncogene-induced premature senescence. The S phase of the cell cycle, polyploidy events, DNA double strand breaks (DSBs) and DNA single strand breaks (SSBs) were increased in BPV-1-positive cells compared to control fibroblasts. BPV-1-mediated oxidative stress may contribute to telomere dysfunction in sarcoid-derived fibroblasts. Loss of mitochondrial membrane potential and concurrent elevation in intracellular ATP production may be a consequence of changes in energy-supplying pathways in BPV-1-positive cells which is also typical for cancer cells. Shifts in energy metabolism may support rapid proliferation in cells infected by BPV-1. Nevertheless, sarcoid-derived fibroblasts representing a heterogeneous cell fraction vary in some aspects of metabolic phenotype due to a dual role of BPV-1 in cell transformation and oncogene-induced premature senescence. This was shown with increased senescence-associated β-galactosidase (SA-β-gal) activity. Taken together, metabolic phenotypes in sarcoid-derived fibroblasts are plastic, which are similar to greater plasticity of cancer tissues than normal tissues.

High exchangeable calcium concentrations in soils on Barro Colorado Island, Panama

The soils on four lithologies (basaltic conglomerates, Bohio; Andesite; volcanoclastic sediments with basaltic agglomerates, Caimito volcanic; foraminiferal limestone, Caimito marine) on Barro Colorado Island (BCI) have high exchangeable Ca concentrations and cation-exchange capacities (CEC) compared to other tropical soils on similar parent material. In the 0–10 cm layer of 24 mineral soils, pH values ranged from 5.7 (Caimito volcanic and Andesite) to 6.5 (Caimito marine), concentrations of exchangeable Ca from 134 mmolc kg− 1 (Caimito volcanic) to 585 mmolc kg− 1 (Caimito marine), and cation exchange capacities from 317 mmolc kg− 1 (Caimito volcanic) to 933 mmolc kg− 1 (Caimito marine). X-ray diffractometry of the fraction < 2 μm revealed that smectites dominated the clay mineral assemblage in soil except on Caimito volcanic, where kaolinite was the dominant clay mineral. Exchangeable Ca concentrations decreased with increasing soil depth except on Caimito marine. The weathering indices Chemical Index of Alteration (CIA), Plagioclase Index of Alteration (PIA) and Weathering Index of Parker (WIP) determined for five soils on all geological formations, suggested that in contrast to expectation the topsoil (0–10 cm) appeared to be the least and the subsoil (50–70 cm) and saprolite (isomorphically weathered rock in the soil matrix) the most weathered. Additionally, the weathering indices indicated depletion of base cations and enrichment of Al-(hydr)oxides throughout the soil profile. Tree species did not have an effect on soil properties. Impeded leaching and the related occurrence of overland flow seem to be important in determining clay mineralogy. Our results suggest that (i) edaphic conditions favor the formation of smectites on most lithologies resulting in high CEC and thus high retention capacity for Ca and (ii) that there is an external source such as dust or sea spray deposition supplying Ca to the soils.

Socio-economic atlas of Kenya: Depicting the national population census by county and sub-location

The Socio-Economic Atlas of Kenya is the first of its kind to offer high-resolution spatial depictions and analyses of data collected in the 2009 Kenya Population and Housing Census . The combination of geographic and socio-eco - nomic data enables policymakers at all levels, development experts, and other interested readers to gain a spatial understanding of dynamics affecting Kenya. Where is the informal economic sector most prominent? Which areas have adequate water and sanitation? Where is population growth being slowed effectively? How do education levels vary throughout the country? And where are poverty rates lowest? Answers to questions such as these, grouped into seven broad themes, are visually illustrated on high-resolution maps. By supplying precise information at the sub-location level and summarizing it at the county level, the atlas facilitates better planning that accounts for local contexts and needs. It is a valuable decision-support tool for government institutions at different administrative levels, educational institutions, and others. Three organizations – two in Kenya and one in Switzerland – worked together to create the atlas: the Kenya National Bureau of Statistics (KNBS), the Nanyuki-based Centre for Training and Integrated Research in ASAL Development (CETRAD), and the Centre for Development and Environment (CDE) at the University of Bern. Close cooperation between KNBS, CETRAD, and CDE maximized synergies and knowledge exchange.

Is mental practice an effective adjunct therapeutic strategy for upper limb motor restoration after stroke?

Stroke is one of the most common conditions requiring rehabilitation, and its motor impairments are a major cause of permanent disability. Hemiparesis is observed by 80% of the patients after acute stroke. Neuroimaging studies showed that real and imagined movements have similarities regarding brain activation, supplying evidence that those similarities are based on the same process. Within this context, the combination of MP with physical and occupational therapy appears to be a natural complement based on neurorehabilitation concepts. Our study seeks to investigate if MP for stroke rehabilitation of upper limbs is an effective adjunct therapy. PubMed (Medline), ISI knowledge (Institute for Scientific Information) and SciELO (Scientific Electronic Library) were terminated on 20 February 2015. Data were collected on variables as follows: sample size, type of supervision, configuration of mental practice, setting the physical practice (intensity, number of sets and repetitions, duration of contractions, rest interval between sets, weekly and total duration), measures of sensorimotor deficits used in the main studies and significant results. Random effects models were used that take into account the variance within and between studies. Seven articles were selected. As there was no statistically significant difference between the two groups (MP vs Control), showed a – 0.6 (95% CI: –1.27 to 0.04), for upper limb motor restoration after stroke. The present meta-analysis concluded that MP is not effective as adjunct therapeutic strategy for upper limb motor restoration after stroke.

Prevalence of potential retrograde embolization pathways in the proximal descending aorta in stroke patients and controls.

BACKGROUND Retrograde diastolic blood flow in the proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick) with brain-supplying supra-aortic arteries may constitute a source of stroke. Yet, data only from high-risk populations (cryptogenic stroke patients with aortic atheroma≥3 mm) regarding the prevalence of this potential stroke mechanism are available. We aimed to quantify the frequency of this mechanism in unselected patients with cryptogenic stroke after routine diagnostics and controls without a history of stroke. METHODS 88 patients (67 stroke patients, 21 cardiac controls) were prospectively included. 3D T1-weighted bright blood MRI of the aorta was applied for the detection of complex DAo atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed measuring time-resolved 3D blood flow in vivo. Potential retrograde embolization pathways were defined as the co-occurrence of complex plaques and retrograde blood flow in the DAo reaching the outlet of (a) the left subclavian artery, (b) the left common carotid artery, or/and (c) the brachiocephalic trunk. The frequency of these pathways was analyzed by importing 2D plaque images into 3D blood flow visualization software. RESULTS Complex DAo plaques were more frequent in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls (19.1%); p=0.039), especially in older patients (29/46 (63.04%) patients≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients<60 years of age with 3 plaques; p<0.001). Contrary to our assumption, retrograde diastolic blood flow at the DAo occurred in every patient irrespective of the existence of plaques with a similar extent in both groups (26±14 vs. 32±18 mm; p=0.114). Therefore, only the higher prevalence of complex DAo plaques in stroke patients resulted in a three times higher frequency of potential retrograde embolization pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p=0.048). CONCLUSIONS This study revealed that retrograde flow in the descending aorta is a common phenomenon not only in stroke patients. The existence of potential retrograde embolization pathways depends mainly on the occurrence of complex plaques in the area 0 to ∼30 mm behind the outlet of the left subclavian artery, which is exposed to flow reversal. In conclusion, we have shown that the frequency of potential retrograde embolization pathways was significantly higher in stroke patients suggesting that this mechanism may play a role in retrograde brain embolism.

In-vivo phase contrast magnetic resonance angiography of the cerebrovascular system: a comparative study with duplex sonography.

PURPOSE Assessment of the cerebral blood flow (CBF) is crucial in the evaluation of patients with steno-occlusive diseases of the arteries supplying the brain for prediction of stroke risk. Quantitative phase contrast magnetic resonance angiography (PC-MRA) can be utilised for noninvasive quantification of CBF. The aim of this study was to validate in-vivo PC-MRA data by comparing them with colour-coded duplex (CCD) sonography in patients with cerebrovascular disease. METHODS AND MATERIALS We examined 24 consecutive patients (mean age 63 years) with stenosis of arteries supplying the brain using PC-MRA and CCD. Velocities were measured in a total of 209 stenotic and healthy arterial segments (110 extra- and 99 intracranial). RESULTS Moderate to good correlation of velocity measurements between both techniques was observed in all six extracranial and five out of seven intracranial segments (p <0.05). Velocities measured with CCD sonography were generally higher than those obtained by PC-MRA. Reversal of flow direction was detected consistently with both methods. CONCLUSION PC-MRA represents a robust, standardised magnetic resonance imaging technique for blood flow measurements within a reasonable acquisition time, potentially evolving as valuable work-up tool for more precise patient stratification for revascularisation therapy. PC-MRA overcomes relevant weaknesses of CCD in being not operator-dependent and not relying on a bone window to assess the intracranial arteries.

Selective Transport of Zinc, Manganese, Nickel, Cobalt and Cadmium in the Root System and Transfer to the Leaves in Young Wheat Plants

• Background and Aims The uptake, translocation and redistribution of the heavy metals zinc, manganese, nickel, cobalt and cadmium are relevant for plant nutrition as well as for the quality of harvested plant products. The long-distance transport of these heavy metals within the root system and the release to the shoot in young wheat (Triticum aestivum ‘Arina’) plants were investigated. • Methods After the application of 65Zn, 54Mn, 63Ni, 57Co and 109Cd for 24 h to one seminal root (the other seminal roots being excised) of 54-h-old wheat seedlings, the labelled plants were incubated for several days in hydroponic culture on a medium without radionuclides. • Key Results The content of 65Zn decreased quickly in the labelled part of the root. After the transfer of 65Zn from the roots to the shoot, a further redistribution in the phloem from older to younger leaves was observed. In contrast to 65Zn, 109Cd was released more slowly from the roots to the leaves and was subsequently redistributed in the phloem to the youngest leaves only at trace levels. The content of 63Ni decreased quickly in the labelled part of the root, moving to the newly formed parts of the root system and also accumulating transiently in the expanding leaves. The 54Mn content decreased quickly in the labelled part of the root and increased simultaneously in leaf 1. A strong retention in the labelled part of the root was observed after supplying 57Co. • Conclusions The dynamics of redistribution of 65Zn, 54Mn, 63Ni, 57Co and 109Cd differed considerably. The rapid redistribution of 63Ni from older to younger leaves throughout the experiment indicated a high mobility in the phloem, while 54Mn was mobile only in the xylem and 57Co was retained in the labelled root without being loaded into the xylem.

Developments in mechanical thrombectomy devices for the treatment of acute ischemic stroke

Several recent prospective randomized controlled trials of endovascular stroke therapy using latest generation thrombectomy devices, so called stent-retrievers, have shown significantly improved clinical outcome compared to the standard treatment with intra-venous thrombolysis using r-tPA alone. Despite some differences in inclusion criteria between these studies, all required non-invasive vessel imaging to proof occlusion of a major brain supplying vessel. Furthermore, in most studies additional imaging techniques were used to exclude patients with already established large cerebral infarction or unfavorable collateral or penumbral status. Patients with small infarct volume, severe neurological deficits and in whom thrombectomy can be initiated within the first 6 hours after symptom onset seem to benefit the most. Therefore, mechanical thrombectomy using stent-retrievers in addition to intra-venous thrombolysis is recommended for the treatment of acute ischemic stroke with proven major vessel occlusion in the anterior circulation.

Investigation of hemodynamics in an in vitro system simulating left ventricular support through the right subclavian artery using 4-dimensional flow magnetic resonance imaging.

OBJECTIVES Left ventricular assist devices are an important treatment option for patients with heart failure alter the hemodynamics in the heart and great vessels. Because in vivo magnetic resonance studies of patients with ventricular assist devices are not possible, in vitro models represent an important tool to investigate flow alterations caused by these systems. By using an in vitro magnetic resonance-compatible model that mimics physiologic conditions as close as possible, this work investigated the flow characteristics using 4-dimensional flow-sensitive magnetic resonance imaging of a left ventricular assist device with outflow via the right subclavian artery as commonly used in cardiothoracic surgery in the recent past. METHODS An in vitro model was developed consisting of an aorta with its supra-aortic branches connected to a left ventricular assist device simulating the pulsatile flow of the native failing heart. A second left ventricular assist device supplied the aorta with continuous flow via the right subclavian artery. Four-dimensional flow-sensitive magnetic resonance imaging was performed for different flow rates of the left ventricular assist device simulating the native heart and the left ventricular assist device providing the continuous flow. Flow characteristics were qualitatively and quantitatively evaluated in the entire vessel system. RESULTS Flow characteristics inside the aorta and its upper branching vessels revealed that the right subclavian artery and the right carotid artery were solely supported by the continuous-flow left ventricular assist device for all flow rates. The flow rates in the brain-supplying arteries are only marginally affected by different operating conditions. The qualitative analysis revealed only minor effects on the flow characteristics, such as weakly pronounced vortex flow caused by the retrograde flow via the brachiocephalic artery. CONCLUSIONS The results indicate that, despite the massive alterations in natural hemodynamics due to the retrograde flow via the right subclavian and brachiocephalic arteries, there are no drastic consequences on the flow in the brain-feeding arteries and the flow characteristics in the ascending and descending aortas. It may be beneficial to adjust the operating condition of the left ventricular assist device to the residual function of the failing heart.

Developmental control of H+/amino acid permease gene expression during seed development of Arabidopsis

Long distance transport of amino acids is mediated by several families of differentially expressed amino acid transporters. The two genes AAP1 and AAP2 encode broad specificity H+-amino acid co-transporters and are expressed to high levels in siliques of Arabidopsis, indicating a potential role in supplying the seeds with organic nitrogen. The expression of both genes is developmentally controlled and is strongly induced in siliques at heart stage of embryogenesis, shortly before induction of storage protein genes. Histochemical analysis of transgenic plants expressing promoter-GUS fusions shows that the genes have non-overlapping expression patterns in siliques. AAP1 is expressed in the endosperm and the cotyledons whereas AAP2 is expressed in the vascular strands of siliques and in funiculi. The endosperm expression of AAP1 during early stages of seed development indicates that the endosperm serves as a transient storage tissue for organic nitrogen. Amino acids are transported in both xylem and phloem but during seed filling are imported only via the phloem. AAP2, which is expressed in the phloem of stems and in the veins supplying seeds, may function in uptake of amino acids assimilated in the green silique tissue, in the retrieval of amino acids leaking passively out of the phloem and in xylem-to-phloem transfer along the path. The promoters provide excellent tools to study developmental, hormonal and metabolic control of nitrogen nutrition during development and may help to manipulate the timing and composition of amino acid import into seeds.