• Feasibility of muscle synergy outcomes in clinics, robotics, and sports: A systematic review

      Taborri, J; Agostini, V; Artemiadis, PK; Ghislieri, M; Jacobs, DA; Roh, J; Rossi, S (2018-01-01)
      Copyright © 2018 Juri Taborri et al. In the last years, several studies have been focused on understanding how the central nervous system controls muscles to perform a specific motor task. Although it still remains an open question, muscle synergies have come to be an appealing theory to explain the modular organization of the central nervous system. Even though the neural encoding of muscle synergies remains controversial, a large number of papers demonstrated that muscle synergies are robust across different tested conditions, which are within a day, between days, within a single subject, and between subjects that have similar demographic characteristics. Thus, muscle synergy theory has been largely used in several research fields, such as clinics, robotics, and sports. The present systematical review aims at providing an overview on the applications of muscle synergy theory in clinics, robotics, and sports; in particular, the review is focused on the papers that provide tangible information for (i) diagnosis or pathology assessment in clinics, (ii) robot-control design in robotics, and (iii) athletes' performance assessment or training guidelines in sports.
    • Fibronectin Mechanobiology Regulates Tumorigenesis

      Wang, K; Seo, BR; Fischbach, C; Gourdon, D; Wang, Karin|0000-0001-7812-2583 (2016-03-01)
      © 2015, The Author(s). Fibronectin (Fn) is an essential extracellular matrix (ECM) glycoprotein involved in both physiological and pathological processes. The structure–function relationship of Fn has been and is still being studied, as changes in its molecular structure are integral in regulating (or dysregulating) its biological activities via its cell, matrix component, and growth factor binding sites. Fn comprises three types of repeating modules; among them, FnIII modules are mechanically unstable domains that may be extended/unfolded upon cell traction and either uncover cryptic binding sites or disrupt otherwise exposed binding sites. Cells assemble Fn into a fibrillar network; its conformational flexibility implicates Fn as a critical mechanoregulator of the ECM. Fn has been shown to contribute to altered stroma remodeling during tumorigenesis. This review will discuss (i) the significance of the structure–function relationship of Fn at both the molecular and the matrix scales, (ii) the role of Fn mechanobiology in the regulation of tumorigenesis, and (iii) Fn-related advances in cancer therapy development.
    • From snake venom’s disintegrins and C-type lectins to anti-platelet drugs

      Lazarovici, P; Marcinkiewicz, C; Lelkes, PI; Lelkes, Peter|0000-0003-4954-3498 (2019-05-01)
      © 2019 by the authors. Licensee MDPI, Basel, Switzerland. Snake venoms are attractive natural sources for drug discovery and development, with a number of substances either in clinical use or in research and development. These drugs were developed based on RGD-containing snake venom disintegrins, which efficiently antagonize fibrinogen activation of αIIbβ3 integrin (glycoprotein GP IIb/IIIa). Typical examples of anti-platelet drugs found in clinics are Integrilin (Eptifibatide), a heptapeptide derived from Barbourin, a protein found in the venom of the American Southeastern pygmy rattlesnake and Aggrastat (Tirofiban), a small molecule based on the structure of Echistatin, and a protein found in the venom of the saw-scaled viper. Using a similar drug discovery approach, linear and cyclic peptides containing the sequence K(R)TS derived from VP12, a C-type lectin protein found in the venom of Israeli viper venom, were used as a template to synthesize Vipegitide, a novel peptidomimetic antagonist of α2β1 integrin, with anti-platelet activity. This review focus on drug discovery of these anti-platelet agents, their indications for clinical use in acute coronary syndromes and percutaneous coronary intervention based on several clinical trials, as well as their adverse effects.
    • Genetic findings in sport-related concussions: potential for individualized medicine?

      McDevitt, Jane; Krynetskiy, Evgeny (2017-03)
      Concussion is a traumatic transient disturbance of the brain. In sport, the initial time and severity of concussion is known giving an opportunity for subsequent analysis. Variability in susceptibility and recovery between individual athletes depends, among other parameters, on genetic factors. The genes-encoding polypeptides that determine incidence, severity and prognosis for concussion are the primary candidates for genetic analysis. Genetic polymorphisms in the genes contributing to plasticity and repair (APOE), synaptic connectivity (GRIN2A), calcium influx (CACNA1E), uptake and deposit of glutamate (SLC17A7) are potential biomarkers of concussion incidence and recovery rate. With catalogued genetic variants, prospective genotyping of athletes at the beginning of their career will allow medical professionals to improve concussion management and return-to-play decisions.
    • Getting started in probabilistic graphical models

      Airoldi, EM; Airoldi, Edoardo|0000-0002-3512-0542 (2007-12-01)
      Probabilistic graphical models (PGMs) have become a popular tool for computational analysis of biological data in a variety of domains. But, what exactly are they and how do they work? How can we use PGMs to discover patterns that are biologically relevant? And to what extent can PGMs help us formulate new hypotheses that are testable at the bench? This Message sketches out some answers and illustrates the main ideas behind the statistical approach to biological pattern discovery. © 2007 Edoardo M. Airoldi.
    • HIV-1 associated dementia: Symptoms and causes

      Ghafouri, M; Amini, S; Khalili, K; Sawaya, BE (2006-05-19)
      Despite the use of highly active antiretroviral therapy (HAART), neuronal cell death remains a problem that is frequently found in the brains of HIV-1-infected patients. HAART has successfully prevented many of the former end-stage complications of AIDS, however, with increased survival times, the prevalence of minor HIV-1 associated cognitive impairment appears to be rising among AIDS patients. Further, HIV-1 associated dementia (HAD) is still prevalent in treated patients as well as attenuated forms of HAD and CNS opportunistic disorders. HIV-associated cognitive impairment correlates with the increased presence in the CNS of activated, though not necessarily HIV-1-infected, microglia and CNS macrophages. This suggests that indirect mechanisms of neuronal injury and loss/death occur in HIV/AIDS as a basis for dementia since neurons are not themselves productively infected by HIV-1. In this review, we discussed the symptoms and causes leading to HAD. Outcome from this review will provide new information regarding mechanisms of neuronal loss in AIDS patients. © 2006 Ghafouri et al; licensee BioMed Central Ltd.
    • Hypervalent iodine reagents in high valent transition metal chemistry

      Sousa E Silva, FC; Tierno, AF; Wengryniuk, SE (2017-05-01)
      Over the last 20 years, high valent metal complexes have evolved from mere curiosities to being at the forefront of modern catalytic method development. This approach has enabled transformations complimentary to those possible via traditional manifolds, most prominently carbon-heteroatom bond formation. Key to the advancement of this chemistry has been the identification of oxidants that are capable of accessing these high oxidation state complexes. The oxidant has to be both powerful enough to achieve the desired oxidation as well as provide heteroatom ligands for transfer to the metal center; these heteroatoms are often subsequently transferred to the substrate via reductive elimination. Herein we will review the central role that hypervalent iodine reagents have played in this aspect, providing an ideal balance of versatile reactivity, heteroatom ligands, and mild reaction conditions. Furthermore, these reagents are environmentally benign, non-toxic, and relatively inexpensive compared to other inorganic oxidants. We will cover advancements in both catalysis and high valent complex isolation with a key focus on the subtle effects that oxidant choice can have on reaction outcome, as well as limitations of current reagents.
    • Individual differences and psychosis-risk screening: Practical suggestions to improve the scope and quality of early identification

      Schiffman, J; Ellman, LM; Mittal, VA (2019-01-01)
      Copyright © 2019 Schiffman, Ellman and Mittal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Approaches to identifying individuals at clinical high-risk (CHR) for psychosis currently do not carefully weigh considerations around individual differences. Effective identification depends on awareness of factors beyond psychopathology as it is reflected in the current literature, such as sensitivity to idiographic circumstances and individual differences. The inability to address contextual factors when employing the status quo method of identification likely contributes to the unacceptably poor accuracy when identifying people at CHR. Individual differences related to factors such as culture, race, comorbidity, and development likely play an important role in accurate identification, and have the potential to improve the validity of approaches intended to identify this population. Tailored approaches to assessment based on an awareness of context, identity, setting, and preferences of clients are possible, and customizing assessment efforts accordingly may be useful for accurate identification of people at CHR. Highlighting the potential for the existing early identification paradigm to marginalize or misunderstand certain groups, we describe how effective identification and ethical diagnosis require sensitivity to individual differences writ large. We suggest that recognizing the importance of these factors advances a more inclusive and accurate approach to identification.
    • Insertional mutagenesis strategies in zebrafish

      Sivasubbu, S; Balciunas, D; Amsterdam, A; Ekker, SC; Balciunas, Darius|0000-0003-1938-3243 (2007-10-31)
      We review here some recent developments in the field of insertional mutagenesis in zebrafish. We highlight the advantages and limitations of the rich body of retroviral methodologies, and we focus on the mechanisms and concepts of new transposon-based mutagenesis approaches under development, including prospects for conditional 'gene trapping' and 'gene breaking' approaches. © 2007 BioMed Central Ltd.
    • Integrating TRPV1 Receptor Function with Capsaicin Psychophysics

      Smutzer, G; Devassy, RK; Smutzer, Gregory S.|0000-0002-4036-5667 (2016-01-01)
      © 2016 Gregory Smutzer and Roni K. Devassy. Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase-mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition.
    • Isoform-and paralog-switching in IR-signaling: When diabetes opens the gates to cancer

      Scalia, P; Giordano, A; Martini, C; Williams, SJ; Giordano, Antonio|0000-0002-5959-016X (2020-12-01)
      © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Insulin receptor (IR) and IR-related signaling defects have been shown to trigger insulin-resistance in insulin-dependent cells and ultimately to give rise to type 2 diabetes in mammalian organisms. IR expression is ubiquitous in mammalian tissues, and its over-expression is also a common finding in cancerous cells. This latter finding has been shown to associate with both a relative and absolute increase in IR isoform-A (IR-A) expression, missing 12 aa in its EC subunit corresponding to exon 11. Since IR-A is a high-affinity transducer of Insulin-like Growth Factor-II (IGF-II) signals, a growth factor is often secreted by cancer cells; such event offers a direct molecular link between IR-A/IR-B increased ratio in insulin resistance states (obesity and type 2 diabetes) and the malignant advantage provided by IGF-II to solid tumors. Nonetheless, recent findings on the biological role of isoforms for cellular signaling components suggest that the preferential expression of IR isoform-A may be part of a wider contextual isoform-expression switch in downstream regulatory factors, potentially enhancing IR-dependent oncogenic effects. The present review focuses on the role of isoform-and paralog-dependent variability in the IR and downstream cellular components playing a potential role in the modulation of the IR-A signaling related to the changes induced by insulin-resistance-linked conditions as well as to their relationship with the benign versus malignant transition in underlying solid tumors.
    • Mammalian microRNAs: A small world for fine-tuning gene expression

      Sevignani, C; Calin, GA; Siracusa, LD; Croce, CM (2006-03-01)
      The basis of eukaryotic complexity is an intricate genetic architecture where parallel systems are involved in tuning gene expression, via RNA-DNA, RNA-RNA, RNA-protein, and DNA-protein interactions. In higher organisms, about 97% of the transcriptional output is represented by noncoding RNA (ncRNA) encompassing not only rRNA, tRNA, introns, 5′ and 3′ untranslated regions, transposable elements, and intergenic regions, but also a large, rapidly emerging family named microRNAs. MicroRNAs are short 20-22-nucleotide RNA molecules that have been shown to regulate the expression of other genes in a variety of eukaryotic systems. MicroRNAs are formed from larger transcripts that fold to produce hairpin structures and serve as substrates for the cytoplasmic Dicer, a member of the RNase III enzyme family. A recent analysis of the genomic location of human microRNA genes suggested that 50% of microRNA genes are located in cancer-associated genomic regions or in fragile sites. This review focuses on the possible implications of microRNAs in post-transcriptional gene regulation in mammalian diseases, with particular focus on cancer. We argue that developing mouse models for deleted and/or overexpressed microRNAs will be of invaluable interest to decipher the regulatory networks where microRNAs are involved. © Springer Science+Business Media, Inc. 2006.
    • Management of Chlamydia trachomatis genital tract infection: Screening and treatment challenges

      Taylor, BD; Haggerty, CL; Taylor, Brandie|0000-0002-8234-1815 (2011-03-21)
      Chlamydia trachomatis is a prevalent sexually transmitted infection that can lead to serious reproductive morbidity. Management and control of C. trachomatis is a challenge, largely due to its asymptomatic nature and our incomplete understanding of its natural history. Although chlamydia screening programs have been implemented worldwide, several countries have observed increasing rates of reported chlamydia cases. We reviewed the literature relating to the long-term complications of C. trachomatis, as well as screening strategies, treatment, and prevention strategies for reducing chlamydia in the population. Articles from 1950-2010 were identified through a Medline search using the keyword "Chlamydia trachomatis" combined with "screening", "pelvic inflammatory disease", "endometritis", "salpingitis", "infertility", "ectopic pregnancy", "urethritis", "epididymitis", "proctitis", "prostatitis", "reinfection", "cost- effectiveness", "treatment", "vaccines", or "prevention". Progression of C. trachomatis varies, and recurrent infections are common. Currently, there is limited evidence on the effectiveness of chlamydia screening. Higher quality studies are needed to determine the efficacy of more frequent screening, on a broader range of sequelae, including infertility and ectopic pregnancy, in addition to pelvic inflammatory disease. Studies should focus on delineating the natural history of recurrent infections, paying particular attention to treatment failures. Furthermore, alternatives to screening, such as vaccines, should continue to be explored. © 2011 Taylor and Haggerty, publisher and licensee Dove Medical Press Ltd.
    • Measuring Nutrition and Food Literacy in Adults: A Systematic Review and Appraisal of Existing Measurement Tools

      Yuen, Eva YN; Thomson, Maria; Gardiner, Heather; Gardiner, Heather Marie|0000-0003-2017-991X (2018-08-01)
      Background: Nutrition literacy (NL) and food literacy (FL) have emerged as key components in the promotion and maintenance of healthy dietary practices. However, a critical appraisal of existing tools is required to advance the operationalization and measurement of these constructs using instruments that demonstrate sound validity and reliability. Methods: Electronic databases were searched in January and July 2016, January 2017, and March 2018 for publications detailing the development and/or testing of NL or FL instruments. Instruments' psychometric properties were assessed using a structured methodological framework. We identified 2,563 new titles and abstracts, and short-listed 524 for full review. The extent to which key domains of NL were included in each measure was examined. Key Results: Thirteen instruments assessing NL underwent full evaluation; seven from the United States, and one each from Australia, Norway, Switzerland, Italy, Hong Kong, and Japan. Measures targeted general Spanish-, Italian-, or Cantonese-speaking adults; primary care patients, parent, and populations with breast cancer. Instruments ranged from 6 to 64 items, and they predominantly assessed functional NL rather than broader domains of NL. Substantial variation in methodological rigor was observed across measures. Discussion: Multidimensional and psychometrically sound measures that capture broader domains of NL and assess FL are needed. Plain Language Summary: This review systemically compiles, and critically appraises 13 existing measures that assess nutrition literacy and food literacy in an adult population. Substantial variation in methodological rigor was found across the measures, and most tools assessed nutrition literacy rather than food literacy. Findings from this current review may be useful to guide development of future measures that comprehensively capture nutrition literacy and food literacy. [HLRP: Health Literacy Research and Practice . 2018;2(3):e134-e160.].
    • Micrornas dysregulation and mitochondrial dysfunction in neurodegenerative diseases

      Catanesi, M; D’angelo, M; Tupone, MG; Benedetti, E; Giordano, A; Castelli, V; Cimini, A; Giordano, Antonio|0000-0002-5959-016X (2020-09-01)
      © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Neurodegenerative diseases are debilitating and currently incurable conditions causing severe cognitive and motor impairments, defined by the progressive deterioration of neuronal structure and function, eventually causing neuronal loss. Understand the molecular and cellular mechanisms underlying these disorders are essential to develop therapeutic approaches. MicroRNAs (miRNAs) are short non-coding RNAs implicated in gene expression regulation at the post-transcriptional level. Moreover, miRNAs are crucial for different processes, including cell growth, signal transmission, apoptosis, cancer and aging-related neurodegenerative diseases. Altered miRNAs levels have been associated with the formation of reactive oxygen species (ROS) and mitochondrial dysfunction. Mitochondrial dysfunction and ROS formation occur in many neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. The crosstalk existing among oxidative stress, mitochondrial dysfunction and miRNAsdysregulation plays a pivotal role in the onset and progression of neurodegenerative diseases. Based on this evidence, in this review, with a focus on miRNAs and their role in mitochondrial dysfunction in aging-related neurodegenerative diseases, with a focus on their potential as diagnostic biomarkers and therapeutic targets.
    • MicroRNAs in rhabdomyosarcoma: Pathogenetic implications and translational potentiality

      Rota, R; Ciarapica, R; Giordano, A; Miele, L; Locatelli, F; Giordano, Antonio|0000-0002-5959-016X (2011-09-24)
      There is growing evidence that interconnections among molecular pathways governing tissue differentiation are nodal points for malignant transformation. In this scenario, microRNAs appear as crucial players. This class of non-coding small regulatory RNA molecules controls developmental programs by modulating gene expression through post-transcriptional silencing of target mRNAs. During myogenesis, muscle-specific and ubiquitously-expressed microRNAs tightly control muscle tissue differentiation. In recent years, microRNAs have emerged as prominent players in cancer as well. Rhabdomyosarcoma is a pediatric skeletal muscle-derived soft-tissue sarcoma that originates from myogenic precursors arrested at different stages of differentiation and that continue to proliferate indefinitely. MicroRNAs involved in muscle cell fate determination appear down-regulated in rhabdomyosarcoma primary tumors and cell lines compared to their normal counterparts. More importantly, they behave as tumor suppressors in this malignancy, as their re-expression is sufficient to restore the differentiation capability of tumor cells and to prevent tumor growth in vivo. In addition, up-regulation of pro-oncogenic microRNAs has also been recently detected in rhabdomyosarcoma.In this review, we provide an overview of current knowledge on microRNAs de-regulation in rhabdomyosarcoma. Additionally, we examine the potential of microRNAs as prognostic and diagnostic markers in this soft-tissue sarcoma, and discuss possible therapeutic applications and challenges of a "microRNA therapy". © 2011 Rota et al; licensee BioMed Central Ltd.
    • Molecular Biology and Evolution of Cancer: From Discovery to Action

      Somarelli, JA; Gardner, H; Cannataro, VL; Gunady, EF; Boddy, AM; Johnson, NA; Fisk, JN; Gaffney, SG; Chuang, JH; Li, S; Ciccarelli, FD; Panchenko, AR; Megquier, K; Kumar, S; Dornburg, A; Degregori, J; Townsend, JP; Kumar, Sudhir|0000-0002-9918-8212 (2020-02-01)
      © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. Cancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or delay cancer evolution - and progression - require a deep understanding of the underlying molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform cancer biology in new and meaningful ways. We also highlight current challenges to applying these concepts, and propose ways in which incorporating these concepts could identify new therapeutic modes and vulnerabilities in cancer.
    • Mycoplasma genitalium: An emerging cause of pelvic inflammatory disease

      Haggerty, CL; Taylor, BD; Taylor, Brandie|0000-0002-8234-1815 (2011-12-01)
      Mycoplasma genitalium is a sexually transmitted pathogen that is increasingly identified among women with pelvic inflammatory disease (PID). Although Chlamydia trachomatis and Neisseria gonorrhoeae frequently cause PID, up to 70% of cases have an unidentified etiology. This paper summarizes evidence linking M. genitalium to PID and its long-term reproductive sequelae. Several PCR studies have demonstrated that M. genitalium is associated with PID, independent of gonococcal and chlamydial infection. Most have been cross-sectional, although one prospective investigation suggested that M. genitalium was associated with over a thirteenfold risk of endometritis. Further, a nested case-control posttermination study demonstrated a sixfold increased risk of PID among M. genitalium positive patients. Whether or not M. genitalium upper genital tract infection results in long-term reproductive morbidity is unclear, although tubal factor infertility patients have been found to have elevated M. genitalium antibodies. Several lines of evidence suggest that M. genitalium is likely resistant to many frequently used PID treatment regimens. Correspondingly, M. genitalium has been associated with treatment failure following cefoxitin and doxycycline treatment for clinically suspected PID. Collectively, strong evidence suggests that M. genitalium is associated with PID. Further study of M. genitalium upper genital tract infection diagnosis, treatment and long-term sequelae is warranted. Copyright © 2011 Catherine L. Haggerty and Brandie D. Taylor.
    • Nuclear export of mRNA molecules studied by SPEED microscopy

      Li, Y; Junod, SL; Ruba, A; Kelich, JM; Yang, W; Yang, Weidong|0000-0002-3554-3035 (2019-01-15)
      © 2018 Temple University The nuclear exit of messenger RNA (mRNA) molecules through the nuclear pore complex (NPC) is an essential step in the translation process of all proteins. The current limitations of conventional fluorescence and electron microscopy have prevented elucidation of how mRNA exports through the NPCs of live cells. In the recent years, various single-molecule fluorescence (SMF) microscopy techniques have been developed to improve the temporal and spatial resolutions of live-cell imaging allowing a more comprehensive understanding of the dynamics of mRNA export through native NPCs. In this review, we firstly evaluate the necessity of single-molecule live-cell microscopy in the study of mRNA nuclear export. Then, we highlight the application of single-point edge-excitation sub-diffraction (SPEED) microscopy that combines high-speed SMF microscopy and a 2D-to-3D transformation algorithm in the studies of nuclear transport kinetics and route for mRNAs. Finally, we summarize the new features of mRNA nuclear export found with SPEED microscopy as well as the reliability and accuracy of SPEED microscopy in mapping the 3D spatial locations of transport routes adopted by proteins and mRNAs through the NPCs.