Motor Synergies Measurement Reveals the Relevant Role of Variability in Reward-Based Learning

Currently, it is not fully understood how motor variability is regulated to ease of motor learning processes during reward-based tasks. This study aimed to assess the potential relationship between different dimensions of motor variability (i.e., the motor variability structure and the motor synergies variability) and the learning rate in a reward-based task developed using a two-axis force sensor in a computer environment. Forty-four participants performed a pretest, a training period, a posttest, and three retests. They had to release a virtual ball to hit a target using a vertical handle attached to a dynamometer in a computer-simulated reward-based task. The participants’ throwing performance, learning ratio, force applied, variability structure (detrended fluctuation analysis, DFA), and motor synergy variability (good and bad variability ratio, GV/BV) were calculated. Participants with higher initial GV/BV displayed greater performance improvements than those with lower GV/BV. DFA did not show any relationship with the learning ratio. These results suggest that exploring a broader range of successful motor synergy combinations to achieve the task goal can facilitate further learning during reward-based tasks. The evolution of the motor variability synergies as an index of the individuals’ learning stages seems to be supported by our study.

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The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽

10.3390/genes12060902 ◽

2021 ◽

Vol 12 (6) ◽

pp. 902

Author(s):

Eva Costanzi ◽

Carolina Simioni ◽

Gabriele Varano ◽

Cinzia Brenna ◽

Ilaria Conti ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Vesicles ◽

Tumor Metastasis ◽

Biological Processes ◽

Rna Molecules ◽

Expression Of Genes ◽

Non Coding Rna ◽

Donor Cells ◽

Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

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The Relevance of the SH2 Domain for c-Src Functionality in Triple-Negative Breast Cancer Cells

Cancers ◽

10.3390/cancers13030462 ◽

2021 ◽

Vol 13 (3) ◽

pp. 462

Author(s):

Víctor Mayoral-Varo ◽

María Pilar Sánchez-Bailón ◽

Annarica Calcabrini ◽

Marta García-Hernández ◽

Valerio Frezza ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Sh2 Domain ◽

Model Systems ◽

System A ◽

Promising Therapeutic Target ◽

Relevant Role ◽

Inactivating Mutation

The role of Src family kinases (SFKs) in human tumors has been always associated with tyrosine kinase activity and much less attention has been given to the SH2 and SH3 adapter domains. Here, we studied the role of the c-Src-SH2 domain in triple-negative breast cancer (TNBC). To this end, SUM159PT and MDA-MB-231 human cell lines were employed as model systems. These cells conditionally expressed, under tetracycline control (Tet-On system), a c-Src variant with point-inactivating mutation of the SH2 adapter domain (R175L). The expression of this mutant reduced the self-renewal capability of the enriched population of breast cancer stem cells (BCSCs), demonstrating the importance of the SH2 adapter domain of c-Src in the mammary gland carcinogenesis. In addition, the analysis of anchorage-independent growth, proliferation, migration, and invasiveness, all processes associated with tumorigenesis, showed that the SH2 domain of c-Src plays a very relevant role in their regulation. Furthermore, the transfection of two different aptamers directed to SH2-c-Src in both SUM159PT and MDA-MB-231 cells induced inhibition of their proliferation, migration, and invasiveness, strengthening the hypothesis that this domain is highly involved in TNBC tumorigenesis. Therefore, the SH2 domain of c-Src could be a promising therapeutic target and combined treatments with inhibitors of c-Src kinase enzymatic activity may represent a new therapeutic strategy for patients with TNBC, whose prognosis is currently very negative.

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Lights and Shadows in the Genetics of Syndromic and Non-Syndromic Hearing Loss in the Italian Population

Genes ◽

10.3390/genes11111237 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1237

Author(s):

Anna Morgan ◽

Stefania Lenarduzzi ◽

Beatrice Spedicati ◽

Elisabetta Cattaruzzi ◽

Flora Maria Murru ◽

...

Keyword(s):

Hearing Loss ◽

Disease Genes ◽

Italian Population ◽

Essential Information ◽

Whole Exome ◽

Relevant Role ◽

Multiplex Ligation Probe Amplification ◽

Syndromic Hearing Loss

Hearing loss (HL), both syndromic (SHL) and non-syndromic (NSHL), is the most common sensory disorder, affecting ~460 million people worldwide. More than 50% of the congenital/childhood cases are attributable to genetic causes, highlighting the importance of genetic testing in this class of disorders. Here we applied a multi-step strategy for the molecular diagnosis of HL in 125 patients, which included: (1) an accurate clinical evaluation, (2) the analysis of GJB2, GJB6, and MT-RNR1 genes, (3) the evaluation STRC-CATSPER2 and OTOA deletions via Multiplex Ligation Probe Amplification (MLPA), (4) Whole Exome Sequencing (WES) in patients negative to steps 2 and 3. Our approach led to the characterization of 50% of the NSHL cases, confirming both the relevant role of the GJB2 (20% of cases) and STRC deletions (6% of cases), and the high genetic heterogeneity of NSHL. Moreover, due to the genetic findings, 4% of apparent NSHL patients have been re-diagnosed as SHL. Finally, WES characterized 86% of SHL patients, supporting the role of already know disease-genes. Overall, our approach proved to be efficient in identifying the molecular cause of HL, providing essential information for the patients’ future management.

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Novel Insights on the Role of Nitric Oxide in the Ovary: A Review of the Literature

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18030980 ◽

2021 ◽

Vol 18 (3) ◽

pp. 980

Author(s):

Maria Cristina Budani ◽

Gian Mario Tiboni

Keyword(s):

Nitric Oxide ◽

In Vivo Studies ◽

Published Data ◽

Vitro Fertilization ◽

Peripheral Neurons ◽

Relevant Role ◽

Oocyte Meiotic Maturation

Nitric oxide (NO) is formed during the oxidation of L-arginine to L-citrulline by the action of multiple isoenzymes of NO synthase (NOS): neuronal NOS (nNOS), endotelial NOS (eNOS), and inducible NOS (iNOS). NO plays a relevant role in the vascular endothelium, in central and peripheral neurons, and in immunity and inflammatory systems. In addition, several authors showed a consistent contribution of NO to different aspects of the reproductive physiology. The aim of the present review is to analyse the published data on the role of NO within the ovary. It has been demonstrated that the multiple isoenzymes of NOS are expressed and localized in the ovary of different species. More to the point, a consistent role was ascribed to NO in the processes of steroidogenesis, folliculogenesis, and oocyte meiotic maturation in in vitro and in vivo studies using animal models. Unfortunately, there are few nitric oxide data for humans; there are preliminary data on the implication of nitric oxide for oocyte/embryo quality and in-vitro fertilization/embryo transfer (IVF/ET) parameters. NO plays a remarkable role in the ovary, but more investigation is needed, in particular in the context of human ovarian physiology.

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Cellular Senescence in Liver Disease and Regeneration

Seminars in Liver Disease ◽

10.1055/s-0040-1722262 ◽

2021 ◽

Author(s):

Sofia Ferreira-Gonzalez ◽

Daniel Rodrigo-Torres ◽

Victoria L. Gadd ◽

Stuart J. Forbes

Keyword(s):

Cell Cycle ◽

Liver Disease ◽

Cell Cycle Arrest ◽

Genomic Instability ◽

Cellular Senescence ◽

Cell Populations ◽

Cycle Arrest ◽

Relevant Role ◽

Extent Of Damage

AbstractCellular senescence is an irreversible cell cycle arrest implemented by the cell as a result of stressful insults. Characterized by phenotypic alterations, including secretome changes and genomic instability, senescence is capable of exerting both detrimental and beneficial processes. Accumulating evidence has shown that cellular senescence plays a relevant role in the occurrence and development of liver disease, as a mechanism to contain damage and promote regeneration, but also characterizing the onset and correlating with the extent of damage. The evidence of senescent mechanisms acting on the cell populations of the liver will be described including the role of markers to detect cellular senescence. Overall, this review intends to summarize the role of senescence in liver homeostasis, injury, disease, and regeneration.

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The role of task-goal attributes in employee performance.

Psychological Bulletin ◽

10.1037/h0036775 ◽

1974 ◽

Vol 81 (7) ◽

pp. 434-452 ◽

Cited By ~ 130

Author(s):

Richard M. Steers ◽

Lyman W. Porter

Keyword(s):

Employee Performance ◽

Task Goal

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Neoplastic conversion of preneoplastic Syrian hamster cells: rate estimation by fluctuation analysis

Molecular and Cellular Biology ◽

10.1128/mcb.3.5.931-945.1983 ◽

1983 ◽

Vol 3 (5) ◽

pp. 931-945

Author(s):

B D Crawford ◽

J C Barrett ◽

P O Ts'o

Keyword(s):

Syrian Hamster ◽

Neoplastic Transformation ◽

Solid Substrate ◽

Established Cell Line ◽

Fluctuation Analysis ◽

Neoplastic Progression ◽

Early Passage

Analysis of the role of gene mutations in the multistep process of neoplastic transformation requires that the discrete steps in carcinogenesis first be dissected. Toward this end, we have isolated and characterized preneoplastic Syrian hamster cells which exhibit in vitro a trait highly correlated with neoplastic conversion in vivo. Previous findings (J. C. Barrett, Cancer Res. 40:91-94, 1980) indicate that spontaneous neoplastic transformation of Syrian hamster cells occurs in at least two steps. An intermediate stage, characterized by an aneuploid established cell line which has a propensity to become neoplastic spontaneously upon further growth in vitro, has been described. These preneoplastic cells differ from diploid early-passage Syrian hamster cells in becoming capable of anchorage-independent growth in semisolid agar, as well as becoming neoplastic in vivo when attached to a solid substrate. Evidence presented here demonstrates that anchorage-independent conversion in vitro is a reliable marker for neoplastic conversion in this cell system. Fluctuation analyses, patterned after those described by Luria and Delbruck for microbial genetics, demonstrate that anchorage-independent variants are generated randomly from clonally derived preneoplastic cells at the rate of 10(-8) to 10(-7) variants per cell per generation. These results establish a multistep stochastic process for transformation in vitro and indicate that conversion to anchorage independence may be necessary for Syrian hamster cells to become tumorigenic. The possible role of gene mutation in this step during neoplastic progression is discussed.

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Design of self-healing catalysts for aircraft application

International Journal of Structural Integrity ◽

10.1108/ijsi-12-2017-0077 ◽

2018 ◽

Vol 9 (6) ◽

pp. 723-736 ◽

Cited By ~ 1

Author(s):

Elisa Calabrese ◽

Pasquale Longo ◽

Carlo Naddeo ◽

Annaluisa Mariconda ◽

Luigi Vertuccio ◽

...

Keyword(s):

Ruthenium Catalysts ◽

The Self ◽

Self Healing ◽

Catalytic Systems ◽

Content Type ◽

Aerospace Applications ◽

Healing Efficiency ◽

Relevant Role ◽

Aircraft Application

PurposeThe purpose of this paper is to highlight the relevant role of the stereochemistry of two Ruthenium catalysts on the self-healing efficiency of aeronautical resins.Design/methodology/approachHere, a very detailed evaluation on the stereochemistry of two new ruthenium catalysts evidences the crucial role of the spatial orientation of phenyl groups in the N-heterocyclic carbene ligands in determining the temperature range within the curing cycles is feasible without deactivating the self-healing mechanisms (ring-opening metathesis polymerization reactions) inside the thermosetting resin. The exceptional activity and thermal stability of the HG2MesPhSyncatalyst, with the syn orientation of phenyl groups, highlight the relevant potentiality and the future perspectives of this complex for the activation of the self-healing function in aeronautical resins.FindingsThe HG2MesPhSyncomplex, with the syn orientation of the phenyl groups, is able to activate metathesis reactions within the highly reactive environment of the epoxy thermosetting resins, cured up to 180°C, while the other stereoisomer, with the anti-orientation of the phenyl groups, does not preserve its catalytic activity in these conditions.Originality/valueIn this paper, a comparison between the self-healing functionality of two catalytic systems has been performed, using metathesis tests and FTIR spectroscopy. In the field of the design of catalytic systems for self-healing structural materials, a very relevant result has been found: a slight difference in the molecular stereochemistry plays a key role in the development of self-healing materials for aeronautical and aerospace applications.

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Blood pressure regulation by ETA and ETB receptors in conscious, telemetry-instrumented mice and role of ETA in hypertension produced by selective ETB blockade

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01221.2005 ◽

2006 ◽

Vol 290 (6) ◽

pp. H2554-H2559 ◽

Cited By ~ 14

Author(s):

Ryan M. Fryer ◽

Pamela A. Rakestraw ◽

Patricia N. Banfor ◽

Bryan F. Cox ◽

Terry J. Opgenorth ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Blood Pressure Regulation ◽

Pressure Regulation ◽

Type B ◽

Selective Antagonist ◽

Relevant Role ◽

Basal Blood Pressure ◽

Baseline Values

The net contribution of endothelin type A (ETA) and type B (ETB) receptors in blood pressure regulation in humans and experimental animals, including the conscious mouse, remains undefined. Thus we assessed the role of ETA and ETB receptors in the control of basal blood pressure and also the role of ETA receptors in maintaining the hypertensive effects of systemic ETB blockade in telemetry-instrumented mice. Mean arterial pressure (MAP) and heart rate were recorded continuously from the carotid artery and daily (24 h) values determined. At baseline, MAP ranged from 99 ± 1 to 101 ± 1 mmHg and heart rate ranged between 547 ± 15 and 567 ± 19 beats/min ( n = 6). Daily oral administration of the ETB selective antagonist A-192621 [10 mg/kg twice daily] increased MAP to 108 ± 1 and 112 ± 2 mmHg on days 1 and 5, respectively. Subsequent coadministration of the ETA selective antagonist atrasentan (5 mg/kg twice daily) in conjunction with A-192621 (10 mg/kg twice daily) decreased MAP to baseline values on day 6 (99 ± 2 mmHg) and to below baseline on day 8 (89 ± 3 mmHg). In a separate group of mice ( n = 6) in which the treatment was reversed, systemic blockade of ETB receptors produced no hypertension in animals pretreated with atrasentan, underscoring the importance of ETA receptors to maintain the hypertension produced by ETB blockade. In a third group of mice ( n = 10), ETA blockade alone (atrasentan; 5 mg/kg twice daily) produced an immediate and sustained decrease in MAP to values below baseline (baseline values = 101 ± 2 to 103 ± 2 mmHg; atrasentan decreased pressure to 95 ± 2 mmHg). Thus these data suggest that ETA and ETB receptors play a physiologically relevant role in the regulation of basal blood pressure in normal, conscious mice. Furthermore, systemic ETB receptor blockade produces sustained hypertension in conscious telemetry-instrumented mice that is absent in mice pretreated with an ETA antagonist, suggesting that ETA receptors maintain the hypertension produced by ETB blockade.

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The challenges of adopting BIM for setting and infrastructure management of University of Minho

E3S Web of Conferences ◽

10.1051/e3sconf/20184802002 ◽

2018 ◽

Vol 48 ◽

pp. 02002 ◽

Cited By ~ 1

Author(s):

Paulo J. S. Cruz ◽

Miguel Azenha

Keyword(s):

Shared Knowledge ◽

Facilities Management ◽

Infrastructure Management ◽

Knowledge Resources ◽

Global Challenge ◽

Modelling Framework ◽

Building Information ◽

Relevant Role ◽

The University

The University of Minho (UMinho) is aware of the relevant role of higher education institutions in the global challenge of sustainability. The integration of sustainability values into its strategy encompasses all the fields of its activity. Taking into account the growing importance of shared knowledge resources as a reliable basis for decisions during infrastructures life cycle, the UMinho is currently undergoing an important process of implementing a ‘Building Information Modelling’ framework (BIM). This paper briefly describes the implementation steps that are current towards such a goal, in particular in terms of facilities management aspects.

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