Robot-aided neurorehabilitation in sub-acute and chronic stroke: Does spontaneous recovery have a limited impact on outcome?

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evaluation of upper limb sense of position in healthy individuals and patients after stroke

The aims of this study were to develop and evaluate reliability of a quantitative assessment tool for upper limb sense of position on the horizontal plane. We evaluated 15 healthy individuals (controls) and 9 stroke patients. A robotic device passively moved one arm of the blindfolded participant who had to actively move his/her opposite hand to the mirror location in the workspace. Upper-limb's position was evaluated by a digital camera. The position of the passive hand was compared with the active hand's 'mirror' position. Performance metrics were then computed to measure the mean absolute errors, error variability, spatial contraction/expansion, and systematic shifts. No significant differences were observed between dominant and non-dominant active arms of controls. All performance parameters of the post-stroke group differed significantly from those of controls. This tool can provide a quantitative measure of upper limb sense of position, therefore allowing detection of changes due to rehabilitation

Nitrogen balance and fate in a heavily impacted watershed (Oglio River, Northern Italy): in quest of the missing sources and sinks

We present data from a comprehensive investigation carried out from 2007 to 2010, focussing on nitrogen pollution in the Oglio River basin (3800 km², Po Plain, Northern Italy). Nitrogen mass balances, computed for the whole basin with 2000 and 2008 data, suggest a large N surplus in this area, over 40 000 t N yr⁻¹, and increasing between 2000 and 2008. Calculations indicate a very large impact of animal husbandry and agricultural activities in this watershed, with livestock manure and synthetic fertilizers contributing 85% of total N inputs (about 100 000 t N yr⁻¹) and largely exceeding crop uptake and other N losses (about 60 000 t N yr⁻¹). Nitrogen from domestic and industrial origin is estimated as about 5800 and 7200 t N yr⁻¹, respectively, although these loads are overestimated, as denitrification in treatment plants is not considered; nonetheless, they represent a minor term of the N budget. Annual export of nitrogen from the basin, calculated from flow data and water chemistry at the mouth of the Oglio River, is estimated at 13 000 t N yr⁻¹, and represents a relatively small fraction of N inputs and surplus (∼12% and 34%, respectively). After considering N sinks in crop uptake, soil denitrification and volatilization, a large excess remains unaccounted (∼26 000 t N yr⁻¹) in unknown temporary or permanent N sinks. Nitrogen removal via denitrification was evaluated in the Oglio riverbed with stable isotope techniques (δ¹⁵N and δ¹⁸O in nitrate). The downstream final segment of the river displays an enriched nitrate stable isotope composition but calculations suggest a N removal corresponding to at most 20% of the unaccounted for N amount. Denitrification was also evaluated in riverine wetlands with the isotope pairing technique. Areal rates are elevated but overall N removal is low (about 1% of the missing N amount), due to small wetland surfaces and limited lateral connectivity. The secondary drainage channel network has a much higher potential for nitrogen removal via denitrification, due to its great linear development, estimated in over 12 500 km, and its capillary distribution in the watershed. In particular, we estimated a maximum N loss up to 8500 t N yr⁻¹, which represents up to 33% of the unaccounted for N amount in the basin. Overall, denitrification in surface aquatic habitats within this basin can be responsible for the permanent removal of about 12 000 t N yr⁻¹; but the fate of some 14 000 t remains unknown. Available data on nitrate concentration in wells suggest that in the central part of the watershed groundwater accumulates nitrogen. Simultaneously, we provide evidences that part of the stored nitrate can be substantially recycled via springs and can pollute surface waters via river-groundwater interactions. This probably explains the ten fold increase of nitrate concentration in a reach of the Oglio River where no point pollutions sources are present

Nitrogen balance and fate in a heavily impacted watershed (Oglio River, Northern Italy): in quest of the missing sources and sinks

Abstract. We present data from a comprehensive investigation carried out from 2007 to 2010, focussing on nitrogen pollution in the Oglio River basin (3800 km2, Po Plain, Northern Italy). Nitrogen mass balances, computed for the whole basin with 2000 and 2008 data, suggest a large N surplus in this area, over 40 000 t N yr−1, and increasing between 2000 and 2008. Calculations indicate a very large impact of animal husbandry and agricultural activities in this watershed, with livestock manure and synthetic fertilizers contributing 85% of total N inputs (about 100 000 t N yr−1) and largely exceeding crop uptake and other N losses (about 60 000 t N yr−1). Nitrogen from domestic and industrial origin is estimated as about 5800 and 7200 t N yr−1, respectively, although these loads are overestimated, as denitrification in treatment plants is not considered; nonetheless, they represent a minor term of the N budget. Annual export of nitrogen from the basin, calculated from flow data and water chemistry at the mouth of the Oglio River, is estimated at 13 000 t N yr−1, and represents a relatively small fraction of N inputs and surplus (∼12% and 34%, respectively). After considering N sinks in crop uptake, soil denitrification and volatilization, a large excess remains unaccounted (∼26 000 t N yr−1) in unknown temporary or permanent N sinks. Nitrogen removal via denitrification was evaluated in the Oglio riverbed with stable isotope techniques (δ15N and δ18O in nitrate). The downstream final segment of the river displays an enriched nitrate stable isotope composition but calculations suggest a N removal corresponding to at most 20% of the unaccounted for N amount. Denitrification was also evaluated in riverine wetlands with the isotope pairing technique. Areal rates are elevated but overall N removal is low (about 1% of the missing N amount), due to small wetland surfaces and limited lateral connectivity. The secondary drainage channel network has a much higher potential for nitrogen removal via denitrification, due to its great linear development, estimated in over 12 500 km, and its capillary distribution in the watershed. In particular, we estimated a maximum N loss up to 8500 t N yr−1, which represents up to 33% of the unaccounted for N amount in the basin. Overall, denitrification in surface aquatic habitats within this basin can be responsible for the permanent removal of about 12 000 t N yr−1; but the fate of some 14 000 t remains unknown. Available data on nitrate concentration in wells suggest that in the central part of the watershed groundwater accumulates nitrogen. Simultaneously, we provide evidences that part of the stored nitrate can be substantially recycled via springs and can pollute surface waters via river-groundwater interactions. This probably explains the ten fold increase of nitrate concentration in a reach of the Oglio River where no point pollutions sources are present

MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.

View the MathML source: Colorectal tumors manifesting high-frequency microsatellite instability (MSI-H) develop genetically as a consequence of mutations in genes harboring repetitive DNA sequences. The activin type 2 receptor (ACVR2), possessing 2 polyadenine coding sequences, was identified as a mutational target, but it is not clear if expression is abrogated. Here, we analyzed MSI-H colorectal cancers for ACVR2 mutation and expression to assess if biallelic inactivation occurs. View the MathML source: All 54 MSI-H colon cancers and 20 random microsatellite stable (MSS) tumors from a population-based cohort of 503 patients were analyzed for mutations in 2 A8 tracts (exon 3 and 10) of ACVR2 and the A10 tract of transforming growth factor \u3b2 receptor 2 (TGFBR2). Additionally, we sequenced exon 10 of ACVR2 in select cancers. ACVR2 expression was determined by immunohistochemistry using an antibody targeting an epitope beyond the predicted truncated protein. View the MathML source: Forty-five of 54 MSI-H cancers (83%) showed mutation (A8 to A7) in the polyadenine tract of exon 10 compared with no MSS tumors. Of tumors with mutant ACVR2, 62% lacked protein expression but all MSS and MSI-H tumors with wild-type ACVR2 expressed protein. We found no evidence of loss of heterozygosity at the ACVR2 locus in MSS tumors. Comparatively, 69% of MSI-H cancers had frameshift mutation in TGFBR2. View the MathML source:ACVR2 mutations are highly frequent in MSI-H colon cancers and in most cases cause loss of ACVR2 expression, indicating biallelic inactivation of the gene. Loss of activin signaling through mutation of ACVR2, similar to observations with TGFBR2, may be important in the genesis of MSI-H colorectal cancer

Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells

The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo

Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16

Multipotent progenitor cells confirm their T cell–lineage identity in the CD4^–CD8^– double-negative (DN) pro-T cell DN2 stages, when expression of the essential transcription factor Bcl11b begins. In vivo and in vitro stage-specific deletions globally identified Bcl11b-controlled target genes in pro-T cells. Proteomics analysis revealed that Bcl11b associated with multiple cofactors and that its direct action was needed to recruit those cofactors to selective target sites. Regions near functionally regulated target genes showed enrichment for those sites of Bcl11b-dependent recruitment of cofactors, and deletion of individual cofactors relieved the repression of many genes normally repressed by Bcl11b. Runx1 collaborated with Bcl11b most frequently for both activation and repression. In parallel, Bcl11b indirectly regulated a subset of target genes by a gene network circuit via the transcription inhibitor Id2 (encoded by Id2) and transcription factor PLZF (encoded by Zbtb16); Id2 and Zbtb16 were directly repressed by Bcl11b, and Id2 and PLZF controlled distinct alternative programs. Thus, our study defines the molecular basis of direct and indirect Bcl11b actions that promote T cell identity and block alternative potentials

Stable isotopes of dissolved nitrate and boron as indicators of the origin and fate of nitrate contamination in groundwater: results from the western Po Plain (Northern Italy).

Stable isotopes of dissolved nitrates and boron represent a powerful tool, complementary to existing monitoring data, enabling the identification of nitrate sources, the assessment of their relative contribution to nitrate pollution and the quantification of nitrate transport and removal processes. This contribution aims to present groundwater isotope data obtained in an area of 15 000 km2 of the western Po plain. Nitrate isotope data show that synthetic fertilisers and anthropogenic organic matter are the main sources of contamination. δ11B allows the discrimination between manure derived and sewage derived contamination. Results indicate that even in agricultural areas, contamination from sewage exists. Samples from the suburban area of Milan, where sewage was considered the most likely source of contamination, show instead a δ11B typical for cattle manure. This study demonstrates that the attribution of the contamination to a source based solely on present-day land use may lead to inappropriate conclusions