• 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.
    • Look for methods, not conclusions

      Bassi, R; Bucci, EM; Calogero, RA; Carninci, P; Ciliberto, G; Conte, P; De Luca, M; Corbellini, G; Giordano, A; Marchionni, L; Massaro Giordano, G; Parini, A; Sbardella, G; Giordano, Antonio|0000-0002-5959-016X (2019-12-01)
    • 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.
    • 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.
    • Parental influences on children's self-regulation of energy intake: Insights from developmental literature on emotion regulation

      Frankel, LA; Hughes, SO; O'Connor, TM; Power, TG; Fisher, JO; Hazen, NL (2012-09-19)
      The following article examines the role of parents in the development of children's self-regulation of energy intake. Various paths of parental influence are offered based on the literature on parental influences on children's emotion self-regulation. The parental paths include modeling, responses to children's behavior, assistance in helping children self-regulate, and motivating children through rewards and punishments. Additionally, sources of variation in parental influences on regulation are examined, including parenting style, child temperament, and child-parent attachment security. Parallels in the nature of parents' role in socializing children's regulation of emotions and energy intake are examined. Implications for future research are discussed. © 2012 Leslie A. Frankel et al.
    • Protein evolution depends on multiple distinct population size parameters

      Platt, A; Weber, CC; Liberles, DA; Liberles, David A|0000-0003-3487-8826 (2018-02-08)
      © 2018 The Author(s). That population size affects the fate of new mutations arising in genomes, modulating both how frequently they arise and how efficiently natural selection is able to filter them, is well established. It is therefore clear that these distinct roles for population size that characterize different processes should affect the evolution of proteins and need to be carefully defined. Empirical evidence is consistent with a role for demography in influencing protein evolution, supporting the idea that functional constraints alone do not determine the composition of coding sequences. Given that the relationship between population size, mutant fitness and fixation probability has been well characterized, estimating fitness from observed substitutions is well within reach with well-formulated models. Molecular evolution research has, therefore, increasingly begun to leverage concepts from population genetics to quantify the selective effects associated with different classes of mutation. However, in order for this type of analysis to provide meaningful information about the intra- and inter-specific evolution of coding sequences, a clear definition of concepts of population size, what they influence, and how they are best parameterized is essential. Here, we present an overview of the many distinct concepts that "population size" and "effective population size" may refer to, what they represent for studying proteins, and how this knowledge can be harnessed to produce better specified models of protein evolution.
    • Role of p53 in the regulation of cellular senescence

      Mijit, M; Caracciolo, V; Melillo, A; Amicarelli, F; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2020-03-01)
      © 2020 by the authors. Licensee MDPI, Basel, Switzerland. The p53 transcription factor plays a critical role in cellular responses to stress. Its activation in response to DNA damage leads to cell growth arrest, allowing for DNA repair, or directs cellular senescence or apoptosis, thereby maintaining genome integrity. Senescence is a permanent cell-cycle arrest that has a crucial role in aging, and it also represents a robust physiological antitumor response, which counteracts oncogenic insults. In addition, senescent cells can also negatively impact the surrounding tissue microenvironment and the neighboring cells by secreting pro-inflammatory cytokines, ultimately triggering tissue dysfunction and/or unfavorable outcomes. This review focuses on the characteristics of senescence and on the recent advances in the contribution of p53 to cellular senescence. Moreover, we also discuss the p53-mediated regulation of several pathophysiological microenvironments that could be associated with senescence and its development.