Advances in experimental medicine and biology (ADV EXP MED BIOL )


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    Advances in experimental medicine and biology, Experimental medicine and biology
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. The human orthologs of most of these 14 proteins affected are stable in the healthy human urinary proteome, and 10 of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics.
    Advances in experimental medicine and biology 01/2015; 845:133-42.
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    ABSTRACT: The fundamental step in brain research deals with recording electroencephalogram (EEG) signals and then investigating the recorded signals quantitatively. Topographic EEG (visual spatial representation of EEG signal) is commonly referred to as brain topomaps or brain EEG maps. In this chapter, full search full search block motion estimation algorithm has been employed to track the brain activity in brain topomaps to understand the mechanism of brain wiring. The behavior of EEG topomaps is examined throughout a particular brain activation with respect to time. Motion vectors are used to track the brain activation over the scalp during the activation period. Using motion estimation it is possible to track the path from the starting point of activation to the final point of activation. Thus it is possible to track the path of a signal across various lobes.
    Advances in experimental medicine and biology 01/2015; 823:159-174.
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    ABSTRACT: Data visualisation is usually a crucial first step in analysing and exploring large-scale complex data. The visualisation of proteomics time-course data on post-translational modifications presents a particular challenge that is largely unmet by existing tools and methods. To this end, we present Minardo, a novel visualisation strategy tailored for such proteomics data, in which data layout is driven by both cellular topology and temporal order. In this work, we utilised the Minardo strategy to visualise a dataset showing phosphorylation events in response to insulin. We evaluated the visualisation together with experts in diabetes and obesity, which led to new insights into the insulin response pathway. Based on this success, we outline how this layout strategy could be automated into a web-based tool for visualising a broad range of proteomics time-course data. We also discuss how the approach could be extended to include protein 3D structure information, as well as higher dimensional data, such as a range of experimental conditions. We also discuss our entry of Minardo in the international DREAM8 competition.
    Advances in experimental medicine and biology 01/2015; 823:3-22.
  • Advances in experimental medicine and biology 01/2015; 842:263-77.
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    ABSTRACT: Physicochemical and molecular properties influence both pharmacokinetic and pharmacodynamic process, as well as drug safety, often in a conflicting way. In this aspect the current trend in drug discovery is to consider ADME (T) properties in parallel with target affinity. The concept of "drug-likeness" defines acceptable boundaries of fundamental properties formulated as simple rules of thumb, in order to aid the medicinal chemist to prioritize drug candidates. Special attention is given to lipophilicity and molecular weight, since there is a tendency for those parameters to increase in regard to complex compounds generated by new technologies, with potential consequences in bioavailability, while high lipophilicity is also associated with undesired effects. Such rules have the advantage to be very simple and are easy to interpret; however their drawback is that they do not take into consideration uncertainties in measurements and calculations as well as the receptor requirements. The case of PPARs, a nuclear receptor family, is discussed in detail in regard to the chemical space covered by the ligands, focusing on the high demands of the ligand binding domain in both lipophilicity and molecular size. Such paradigms indicate that it would be more appropriate to adapt drug-like properties according to specific drug discovery projects.
    Advances in experimental medicine and biology 01/2015; 822:187-94.
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    ABSTRACT: This research explores the satisfaction gap between the expectations of medical doctors when using the Internet to search for health-related information, and the confirmations they receive following the use of specific information sources to meet their information needs. We executed a quantitative study on 303 medical doctors to capture their online information-seeking behavior. Results suggest that authoritative online information sources are strongly related with the derived satisfaction of medical doctors' online information needs, whilst expectation fulfillment is not related with usage of non-authoritative sources. Nevertheless, doctors' perceptions regarding the information quality of online sources, and discerning personal constraints regarding Internet use, moderate the relationship between online source usage and the effectuation of their expectations.
    Advances in experimental medicine and biology 01/2015; 820:217-28.
  • Advances in experimental medicine and biology 01/2015; 842:79-108.
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    ABSTRACT: In the present work, some new 5-[2(3)-dialkylamino alkoxy] Indole 3-thiosemicarbazone 2-ones and 5-[2(3)-dialkylamino alkoxy] Indole 3-hydrazone 2-one were prepared from 5-hydroxy isatin. The structures of the products were characterized by IR, NMR, and MASS Spectral studies. All the compounds were examined for antiepileptic activity by maximal electroshock seizure (MES) and pentylenetetrazole (PTZ) induced convulsion method. These compounds were also evaluated for their neurotoxicity study by rotarod method. Some of these compounds showed good antiepileptic activity when compared with standard drug Phenytoin and all the compounds showed less neurotoxicity when compared with standard drug Diazepam.
    Advances in experimental medicine and biology 01/2015; 822:119-28.
  • Advances in experimental medicine and biology 01/2015; 821:1.
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    ABSTRACT: Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disease that slowly destroys memory and thinking skills. It is the most common cause of dementia among older people. One of the most important hallmarks of AD is the presence of amyloid beta (Aβ) peptide in the brain that suggests that it is the primary trigger for neuronal loss. Herbal extracts have been studied over the years for their potential therapeutic effect in AD. Resveratrol (RSV), one of the most important phytoestrogens, is considered to be useful as estrogen plays an important role in AD. One of the most important amyloid degrading enzymes is neprilysin (NEP), which plays a major role in degrading Aβ, and mainly affected by estrogen. So, the aim of the present study is investigating the possible role of resveratrol in lipopolysaccharide model of AD and the implication of its possible role in regulating the estradiol and neprilysin pathways. Mice were divided into four groups: Control group (0.9 % saline), LPS group (0.8 mg/kg i.p once), Treatment group with RSV (mice were once injected with LPS then after 30 min given a dose of {4 mg/kg} RSV for 7 days), and RSV group only (mice received 4 mg/kg i.p for 7 days only). After 7 days mice were subjected to different behavioral tests using Y-maze, object recognition test, and open field tests. Estradiol and NEP level were measured using ELISA kit. Results showed RSV was able to reverse the decline in different types of memory (working, nonspatial, and locomotor functions) caused by LPS induction in mice. Moreover RSV was able to significantly increase both the estradiol level and NEP level and that may have a great role to decrease Aβ deposition as it has been confirmed that there is a link between NEP and estradiol level; by upregulation of estradiol level this consequently leads to increase in the level of NEP level, and by increasing the NEP level in brain, this lead to decrease in Aβ deposition and enhancing its degradation by NEP.
    Advances in experimental medicine and biology 01/2015; 822:107-18.
  • Advances in experimental medicine and biology 01/2015; 821:3-4.
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    ABSTRACT: Dysregulation of the signaling pathways that govern lactotrope biology contributes to tumorigenesis of prolactin (PRL)-secreting adenomas, or prolactinomas, leading to a state of pathological hyperprolactinemia. Prolactinomas cause hypogonadism, infertility, osteoporosis, and tumor mass effects, and are the most common type of neuroendocrine tumor. In this review, we highlight signaling pathways involved in lactotrope development, homeostasis, and physiology of pregnancy, as well as implications for signaling pathways in pathophysiology of prolactinoma. We also review mutations found in human prolactinoma and briefly discuss animal models that are useful in studying pituitary adenoma, many of which emphasize the fact that alterations in signaling pathways are common in prolactinomas. Although individual mutations have been proposed as possible driving forces for prolactinoma tumorigenesis in humans, no single mutation has been clinically identified as a causative factor for the majority of prolactinomas. A better understanding of lactotrope-specific responses to intracellular signaling pathways is needed to explain the mechanism of tumorigenesis in prolactinoma.
    Advances in experimental medicine and biology 01/2015; 846:37-59.
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    ABSTRACT: Poor oral hygiene, ethanol consumption, and human papillomavirus (HPV) are associated with oral and esophageal cancers. However, the mechanism is not fully known. This study examines alcohol metabolism in Streptococcus and its interaction with HPV-16 in the malignant transformation of oral keratinocytes. The acetaldehyde-producing strain Streptococcus gordonii V2016 was analyzed for adh genes and activities of alcohol and aldehyde dehydrogenases. Streptococcus attachment to immortalized HPV-16 infected human oral keratinocytes, HOK (HPV/HOK-16B), human oral buccal keratinocytes, and foreskin keratinocytes was studied. Acetaldehyde, malondialdehyde, DNA damage, and abnormal proliferation among keratinocytes were also quantified. We found that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB, and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol, and ethanol, respectively. S. gordonii V2016 did not show a detectable aldehyde dehydrogenase. AdhE is the major alcohol dehydrogenase in S. gordonii. Acetaldehyde and malondialdehyde production from permissible Streptococcus species significantly increased the bacterial attachment to keratinocytes, which was associated with an enhanced expression of furin to facilitate HPV infection and several malignant phenotypes including acetaldehyde adduct formation, abnormal proliferation, and enhanced migration through integrin-coated basement membrane by HPV-infected oral keratinocytes. Therefore, expression of multiple alcohol dehydrogenases with no functional aldehyde dehydrogenase contributes to excessive production of acetaldehyde from ethanol by oral streptococci. Oral Streptococcus species and HPV may cooperate to transform oral keratinocytes after ethanol exposure. These results suggest a significant clinical interaction, but further validation is warranted.
    Advances in experimental medicine and biology 01/2015; 815:239-64.
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    ABSTRACT: Urine is a biological material that can be easily obtained in the clinic. The identification of proteins excreted in urine provides useful biological information about the kidney as well as a unique opportunity to examine physiological and pathological changes in the kidney in a noninvasive manner. Recent technological advances in urinary proteomic profiling have provided the foundation for a number of urinary proteomic studies directed at identifying markers of kidney disease diagnosis, prognosis, or responsiveness to therapy. In this review, we describe the strengths of different urinary proteomic methods for the discovery of potential biomarkers of kidney diseases. We also highlight the limitations and future goals of these approaches.
    Advances in experimental medicine and biology 01/2015; 845:151-65.
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    ABSTRACT: Neonates in intensive care units often require supporting medical devices and antibiotic treatment. The intensive care treatment combined with their immature immune system, the increased permeability of mucosa, and the undeveloped microflora of the gut may render the neonates highly vulnerable to colonisation and subsequent infections when exposed to opportunistic pathogens. These infections may not only be local gastrointestinal infections, but also systematic following translocation from the gastrointestinal system. This could be particularly alarming considering that common antibiotics may not be effective if the causative strain is multi-drug resistant.This chapter reviews our information on the microbial colonization of neonatal feeding tubes. The range of organisms which have been recovered are wide, and while primarily bacterial, fungi such as Candida have also been found. The bacteria are principally Staphylococcus spp. and Enterobacteriaceae. The Enterobacteriaceae isolates are predominantly Enterobacter cancerogenus, Serratia marcescens, Enterobacter hormaechei, Escherichia coli and Klebsiella pneumoniae. Many of these isolates encode for antibiotic resistance; E. hormaechei (ceftazidine and cefotaxime) and S. marcescens strains (amoxicillin and co-amoxiclav).
    Advances in experimental medicine and biology 01/2015; 830:113-21.
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    ABSTRACT: Biofilms are complex microbial communities that grow on various surfaces in nature. The oral micobiota tend to form polymicrobial biofilms, particularly on the hard mineralized surfaces of teeth, which may impact on oral health and disease. They can cause inflammation of the adjacent tooth-supporting (periodontal) tissues, leading to destructive periodontal disease and tooth loss. The emergence of osseointegrated dental implants as a restorative treatment option for replacing missing teeth has also brought along new artificial surfaces within the oral cavity, on which oral bacteria can form biofilms. As in the case of natural teeth, biofilms on implant surfaces may also trigger infection and cause inflammatory destruction of the peri-implant tissue (i.e. peri-implantitis). While there are strong similarities in the composition of the mixed microbial flora between periodontal and peri-implant infections, there are also a few distinctive differences. The immunological events underlying the pathogenesis of peri-implant infections are qualitatively similar, yet more extensive, compared to periodontal infections, resulting in a faster progression of tissue destruction. This chapter summarizes the current knowledge on the microbiology and immunology of peri-implant infections, including findings from the peri-implant crevicular fluid, the inflammatory exudate of the peri-implant tissue. Moreover, it discusses the diagnosis and current approaches for the treatment of oral infections.
    Advances in experimental medicine and biology 01/2015; 830:69-84.
  • Advances in experimental medicine and biology 01/2015; 831:45-52.
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    ABSTRACT: We developed a program JVM (Java Visual Mapping) for mapping next generation sequencing read to reference sequence. The program is implemented in Java and is designed to deal with millions of short read generated by sequence alignment using the Illumina sequencing technology. It employs seed index strategy and octal encoding operations for sequence alignments. JVM is useful for DNA-Seq, RNA-Seq when dealing with single-end resequencing. JVM is a desktop application, which supports reads capacity from 1 MB to 10 GB.
    Advances in experimental medicine and biology 01/2015; 827:11-8.
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    ABSTRACT: Large biomolecules are involved in many important biological processes. It would be difficult to use large-scale atomistic molecular dynamics (MD) simulations to study the functional motions of these systems because of the computational expense. Therefore various coarse-grained (CG) approaches have attracted rapidly growing interest, which enable simulations of large biomolecules over longer effective timescales than all-atom MD simulations. The first issue in CG modeling is to construct CG maps from atomic structures. In this chapter, we review the recent development of a novel and systematic method for constructing CG representations of arbitrarily complex biomolecules, in order to preserve large-scale and functionally relevant essential dynamics (ED) at the CG level. In this ED-CG scheme, the essential dynamics can be characterized by principal component analysis (PCA) on a structural ensemble, or elastic network model (ENM) of a single atomic structure. Validation and applications of the method cover various biological systems, such as multi-domain proteins, protein complexes, and even biomolecular machines. The results demonstrate that the ED-CG method may serve as a very useful tool for identifying functional dynamics of large biomolecules at the CG level.
    Advances in experimental medicine and biology 01/2015; 827:33-48.
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    ABSTRACT: Intrinsically disordered proteins lack stable tertiary and/or secondary structures under physiological conditions in vitro. Intrinsically disordered proteins undergo significant conformational transitions to well folded forms only on binding to partner. Molecular dynamics simulations are used to research the mechanism of folding for intrinsically disordered protein upon partner binding. Room-temperature MD simulations suggest that the intrinsically disordered proteins have nonspecific and specific interactions with the partner. Kinetic analysis of high-temperature MD simulations shows that bound and apo-states unfold via a two-state process, respectively. Φ-value analysis can identify the key residues of intrinsically disordered proteins. Kolmogorov-Smirnov (KS) P test analysis illustrates that the specific recognition between intrinsically disordered protein and partner might follow induced-fit mechanism. Furthermore, these methods can be widely used for the research of the binding induced folding for intrinsically disordered proteins.
    Advances in experimental medicine and biology 01/2015; 827:111-21.