Effects of chronic exercise on severity, quality of life and functionality in an elderly Parkinson’s disease patient: case report

Exercise produces potential influences on physical and mental capacity in patients with neuropsychiatric disor- ders, and can be made a viable form of therapy to treat Parkinson’s disease (PD). We report the chronic effects of a regu- lar physical exercise protocol on cognitive and motor functions, functional capacity, and symptoms in an elderly PD pa- tient without dementia. The patient participated of a program composed of proprioceptive, aerobic and flexibility exer- cises, during 1 hour, three days a week, for nine months. Patient used 600 mg of L-DOPA daily, and 1 hour prior to each exercise session. Assessment was conducted in three stages, 0-3, 3-6 and 6 to 9 months, using percentual variation to the scales Hoehn and Yahr, Mini-Mental State Examination (MMSE), Parkinson Activity Scale (PAS), Beck Depression In- ventory (BDI), and Unified Parkinson's Disease Rating Scale (UPDRS-III). Reassessment showed clear changes in clini- cal parameters for Hoehn and Yahr (4 to 2.5), MMSE (14 to 22), PAS (13 to 29), BDI (9 to 7) and UPDRS-III (39 to 27) at the end of 9 months. According to our data, exercise seems to be effective in promoting the functional capacity and the maintenance of cognitive and motor functions of PD patients. Regular exercise protocols can be implemented as an ad- junctive treatment for reducing the severity of PD

Heuristics-based detection to improve text/graphics segmentation in complex engineering drawings.

The demand for digitisation of complex engineering drawings becomes increasingly important for the industry given the pressure to improve the efficiency and time effectiveness of operational processes. There have been numerous attempts to solve this problem, either by proposing a general form of document interpretation or by establishing an application dependant framework. Moreover, text/graphics segmentation has been presented as a particular form of addressing document digitisation problem, with the main aim of splitting text and graphics into different layers. Given the challenging characteristics of complex engineering drawings, this paper presents a novel sequential heuristics-based methodology which is aimed at localising and detecting the most representative symbols of the drawing. This implementation enables the subsequent application of a text/graphics segmentation method in a more effective form. The experimental framework is composed of two parts: first we show the performance of the symbol detection system and then we present an evaluation of three different state of the art text/graphic segmentation techniques to find text on the remaining image

The role of climate, marine influence and sedimentation rates in late-Holocene estuarine evolution (SW Portugal)

Estuaries are sensitive to changes in global to regional sea level, to climate-driven variation in rainfall and to fluvial discharge. In this study, we use source and environmentally sensitive proxies together with radiocarbon dating to examine a 7-m-thick sedimentary record from the Sado estuary accumulated throughout the last 3.6 kyr. The lithofacies, geochemistry and diatom assemblages in the sediments accumulated between 3570 and 3240 cal. BP indicate a mixture between terrestrial and marine sources. The relative contribution of each source varied through time as sedimentation progressed in a low intertidal to high subtidal and low-energy accreting tidal flat. The sedimentation proceeded under a general pattern of drier and higher aridity conditions, punctuated by century-long changes of the rainfall regime that mirror an increase in storminess that affected SW Portugal and Europe. The sediment sequence contains evidence of two periods characterized by downstream displacement of the estuarine/freshwater transitional boundary, dated to 3570-3400 cal. BP and 3300-3240 cal. BP. These are intercalated by one episode where marine influence shifted upstream. All sedimentation episodes developed under high terrestrial sediment delivery to this transitional region, leading to exceptionally high sedimentation rates, independently of the relative expression of terrestrial/marine influences in sediment facies. Our data show that these disturbances are mainly climate-driven and related to variations in rainfall and only secondarily with regional sea-level oscillations. From 3240 cal. BP onwards, an abrupt change in sediment facies is noted, in which the silting estuarine bottom reaches mean sea level and continued accreting until present under prevailing freshwater conditions, the tidal flat changing to an alluvial plain. The environmental modification is accompanied by a pronounced change in sedimentation rate that decreased by two orders of magnitude, reflecting the loss of accommodation space rather than the influence of climate or regional sea-level drivers.FCT by Spanish Ministry of Science and Innovation [SFRH/BD/110270/2015, HAR2014-51830-P, HAR2011-29907-C03-00]FCTPortuguese Foundation for Science and Technology [PTDC/HISARQ/121592/2010]Instituto Dom Luiz-IDL [UID/GEO/50019/2013]info:eu-repo/semantics/publishedVersio

Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci

BACKGROUND: The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider promoter conservation and positional conservation as indicators of functional commonality. RESULTS: We identify 665 conserved lncRNA promoters in mouse and human that are preserved in genomic position relative to orthologous coding genes. These positionally conserved lncRNA genes are primarily associated with developmental transcription factor loci with which they are coexpressed in a tissue-specific manner. Over half of positionally conserved RNAs in this set are linked to chromatin organization structures, overlapping binding sites for the CTCF chromatin organiser and located at chromatin loop anchor points and borders of topologically associating domains (TADs). We define these RNAs as topological anchor point RNAs (tapRNAs). Characterization of these noncoding RNAs and their associated coding genes shows that they are functionally connected: they regulate each other’s expression and influence the metastatic phenotype of cancer cells in vitro in a similar fashion. Furthermore, we find that tapRNAs contain conserved sequence domains that are enriched in motifs for zinc finger domain-containing RNA-binding proteins and transcription factors, whose binding sites are found mutated in cancers. CONCLUSIONS: This work leverages positional conservation to identify lncRNAs with potential importance in genome organization, development and disease. The evidence that many developmental transcription factors are physically and functionally connected to lncRNAs represents an exciting stepping-stone to further our understanding of genome regulation

Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. METHODS Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. RESULTS Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). CONCLUSION Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during childhood.Part of the studies were financed by grants from the Swedish Research Council and from the King Gustaf V and Queen Victoria Research Fund and by grants from Grupos de Investigacion y Desarrollo Tecnologico de la Junta de Andalucia (Grupo consolidado CTS- 159).Ye

P130Cas Attenuates Epidermal Growth Factor (EGF) Receptor Internalization by Modulating EGF-Triggered Dynamin Phosphorylation

BACKGROUND: Endocytosis controls localization-specific signal transduction via epidermal growth factor receptor (EGFR), as well as downregulation of that receptor. Extracellular matrix (ECM)-integrin coupling induces formation of macromolecular complexes that include EGFR, integrin, Src kinase and p130Cas, resulting in EGFR activation. In addition, cell adhesion to ECM increases EGFR localization at the cell surface and reduces EGFR internalization. The molecular mechanisms involved are not yet well understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the molecular mechanism by which p130Cas affects the endocytic regulation of EGFR. Biochemical quantification revealed that cell adhesion to fibronectin (FN) increases total EGFR levels and its phosphorylation, and that p130Cas is required for this process. Measurements of Texas Red-labeled EGF uptake and cell surface EGFR revealed that p130Cas overexpression reduces EGF-induced EGFR internalization, while p130Cas depletion enhances it. In addition, both FN-mediated cell adhesion and p130Cas overexpression reduce EGF-stimulated dynamin phosphorylation, which is necessary for EGF-induced EGFR internalization. Coimmunoprecipitation and GST pull-down assays confirmed the interaction between p130Cas and dynamin. Moreover, a SH3-domain-deleted form of p130Cas, which shows diminished binding to dynamin, inhibits dynamin phosphorylation and EGF uptake less effectively than wild-type p130Cas. CONCLUSIONS/SIGNIFICANCE: Our results show that p130Cas plays an inhibitory role in EGFR internalization via its interaction with dynamin. Given that the EGFR internalization process determines signaling density and specificity in the EGFR pathway, these findings suggest that the interaction between p130Cas and dynamin may regulate EGFR trafficking and signaling in the same manner as other endocytic regulatory proteins related to EGFR endocytosis

Description of the methodology used in an ongoing pediatric care interventional study of children born with cleft lip and palate in South America [NCT00097149]

BACKGROUND: The contribution of birth defects, including cleft lip and palate, to neonatal and infant mortality and morbidity is substantial. As other mortality and morbidity causes including infections, hygiene, prematurity, and nutrition are eradicated in less developed countries, the burden of birth defects will increase proportionally. METHODS/DESIGN: We are using cleft lip and palate as a sentinel birth defect to evaluate its burden on neonatal and infant health and to assess the effectiveness of systematic pediatric care during the first month and first two years of life in decreasing this burden. The neonatal intervention, consisting of weekly pediatric evaluation and referral to appropriate care, is delivered to about 696 infants born with cleft lip and/or palate in 47 hospitals in South America. Neonatal mortality in this group will be compared to that in a retrospective control group of about 464 infants born with cleft lip and/or palate in the same hospitals. The subgroup of infants with isolated clefts of both the lip and palate (about 264) is also randomized into two groups, intervened and non-intervened, and further followed up over 2 years. Intervened cases are evaluated by pediatricians every three months and referred for appropriate care. The intervened and non-intervened cases will be compared over study outcomes to evaluate the intervention effectiveness. Non-intervened cases are matched and compared to healthy controls to assess the burden of cleft lip and palate. Outcomes include child's neurological and physical development and family social and economic conditions. DISCUSSION: Large-scale clinical trials to improve infant health in developing countries are commonly suggested, making it important to share the methods used in ongoing studies with other investigators implementing similar research. We describe here the content of our ongoing pediatric care study in South America. We hope that this may help researchers targeting this area to plan their studies more effectively and encourage the development of similar research efforts to target other birth defects or infant outcomes such as prematurity and low birth weight

Drug-Selected Human Lung Cancer Stem Cells: Cytokine Network, Tumorigenic and Metastatic Properties

Background: Cancer stem cells (CSCs) are thought to be responsible for tumor regeneration after chemotherapy, although direct confirmation of this remains forthcoming. We therefore investigated whether drug treatment could enrich and maintain CSCs and whether the high tumorogenic and metastatic abilities of CSCs were based on their marked ability to produce growth and angiogenic factors and express their cognate receptors to stimulate tumor cell proliferation and stroma formation. Methodology/Findings: Treatment of lung tumor cells with doxorubicin, cisplatin, or etoposide resulted in the selection of drug surviving cells (DSCs). These cells expressed CD133, CD117, SSEA-3, TRA1-81, Oct-4, and nuclear β-catenin and lost expression of the differentiation markers cytokeratins 8/18 (CK 8/18). DSCs were able to grow as tumor spheres, maintain self-renewal capacity, and differentiate. Differentiated progenitors lost expression of CD133, gained CK 8/18 and acquired drug sensitivity. In the presence of drugs, differentiation of DSCs was abrogated allowing propagation of cells with CSC-like characteristics. Lung DSCs demonstrated high tumorogenic and metastatic potential following inoculation into SCID mice, which supported their classification as CSCs. Luminex analysis of human and murine cytokines in sonicated lysates of parental- and CSC-derived tumors revealed that CSC-derived tumors contained two- to three-fold higher levels of human angiogenic and growth factors (VEGF, bFGF, IL-6, IL-8, HGF, PDGF-BB, G-CSF, and SCGF-β). CSCs also showed elevated levels of expression of human VEGFR2, FGFR2, CXCR1, 2 and 4 receptors. Moreover, human CSCs growing in SCID mice stimulated murine stroma to produce elevated levels of angiogenic and growth factors. Conlusions/Significance: These findings suggest that chemotherapy can lead to propagation of CSCs and prevention of their differentiation. The high tumorigenic and metastatic potentials of CSCs are associated with efficient cytokine network production that may represent a target for increased efficacy of cancer therapy. © 2008 Levina et al