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

Publications in this journal

• Article: Lipopolysaccharide's role in the association of Salmonella cells to the mouse intestine studied by ribosomal in situ hybridization. Krogfelt KA, Licht TR, Molin S. Adv Exp Med Biol. 1996;408:123-8. Review.

  Krogfelt KA, Licht TR, Molin S
  Advances in experimental medicine and biology 02/2013;
• Article: Epigenetic control of germline development.

  Priscilla M Van Wynsberghe, Eleanor M Maine
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  ABSTRACT: Dynamic regulation of histone modifications and small noncoding RNAs is observed throughout the development of the C. elegans germ line. Histone modifications are differentially regulated in the mitotic vs meiotic germ line, on X chromosomes vs autosomes and on paired chromosomes vs unpaired chromosomes. Small RNAs function in transposon silencing and developmental gene regulation. Histone modifications and small RNAs produced in the germ line can be inherited and impact embryonic development. Disruption of histone-modifying enzymes or small RNA machinery in the germ line can result in sterility due to degeneration of the germ line and/or an inability to produce functional gametes.
  Advances in experimental medicine and biology 01/2013; 757:373-403.
• Article: Effect of spinal anesthesia for elective cesarean section on cerebral blood oxygenation changes: comparison of hyperbaric and isobaric bupivacaine.

  Yuko Kondo, Kaoru Sakatani, Noriya Hirose, Takeshi Maeda, Jitsu Kato, Setsuro Ogawa, Yoichi Katayama
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  ABSTRACT: We used near-infrared spectroscopy (NIRS) to evaluate cerebral blood oxygenation changes in subjects undergoing cesarean section under spinal anesthesia (SP) with hyperbaric bupivacaine (group H, 27 subjects) or isobaric bupivacaine (group I, 15 subjects). In group H, total-Hb, oxy-Hb, and mean blood pressure (MBP) within 20 min after SP were significantly lower than the baseline values. In contrast, there was no significant change from baseline in total-Hb, oxy-Hb, or MBP in group I after SP. Total-Hb and MBP in group H were significantly lower than those in group I within 10 min after SP. There was no significant change of deoxy-Hb, tissue oxygen index, or heart rate from baseline in either of the groups. These results suggest that isobaric bupivacaine may be superior to hyperbaric bupivacaine for preventing a decrease of maternal cerebral blood flow after SP for cesarean section.
  Advances in experimental medicine and biology 01/2013; 765:109-14.
• Article: Targeted therapy of multiple myeloma.

  Nathan G Dolloff, Giampaolo Talamo
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  ABSTRACT: Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.
  Advances in experimental medicine and biology 01/2013; 779:197-221.
• Article: Emerging molecular therapies for the treatment of acute lymphoblastic leukemia.

  Monali Vasekar, Joshua E Allen, Jamal Joudeh, David Claxton
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  ABSTRACT: The improved molecular understanding of cancer initiation, progression, and therapeutic resistance has yielded several novel molecular events that are being targeted by emerging therapies. While the treatment of ALL is a success story in the pediatric population, achieving a sustained remission in the adult population remains an area of investigation. Nevertheless, certain therapies have significantly improved the overall survival for adult ALL patients that should continue to improve with the discovery of better molecular targets and targeted agents. Here, we discuss novel therapeutic options under clinical investigation for the treatment of Philadephia chromosome negative ALL including immunotherapy, monoclonal antibodies, and small molecules that may be used as single agent or adjuvant therapy in the management of adult ALL.
  Advances in experimental medicine and biology 01/2013; 779:341-58.
• Article: Model-based and model-free mechanisms of human motor learning.

  Adrian M Haith, John W Krakauer
  Advances in experimental medicine and biology 01/2013; 782:1-21.
• Article: Post-transcriptional Stimulation of Gene Expression by MicroRNAs.

  Sooncheol Lee, Shobha Vasudevan
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  ABSTRACT: MicroRNAs are small noncoding RNA regulatory molecules that control gene expression by guiding associated effector complexes to other RNAs via sequence-specific recognition of target sites. Misregulation of microRNAs leads to a wide range of diseases including cancers, inflammatory and developmental disorders. MicroRNAs were found to mediate deadenylation-dependent decay and translational repression of messages through partially complementary microRNA target sites in the 3'-UTR (untranslated region). A growing series of studies has demonstrated that microRNAs and their associated complexes (microRNPs) elicit alternate functions that enable stimulation of gene expression in addition to their assigned repressive roles. These reports, discussed in this chapter, indicate that microRNA-mediated effects via natural 3' and 5'-UTRs can be selective and controlled, dictated by the RNA sequence context, associated complex, and cellular conditions. Similar to the effects of repression, upregulated gene expression by microRNAs varies from small refinements to significant amplifications in expression. An emerging theme from this literature is that microRNAs have a versatile range of abilities to manipulate post-transcriptional control mechanisms leading to controlled gene expression. These studies reveal new potentials for microRNPs in gene expression control that develop as responses to specific cellular conditions.
  Advances in experimental medicine and biology 01/2013; 768:97-126.
• Article: Multifaceted Kinetics of Immuno-Evasion from Tumor Dormancy.

  Alberto d'Onofrio
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  ABSTRACT: Tumor progression is subject to modulation by the immune system. The immune system can eliminate tumors or keep them at a dormant equilibrium size, while some tumors escape immunomodulation and advance to malignancy. Herein, we discuss some aspects of immune evasion of dormant tumors from a theoretical biophysics point of view that can be modeled mathematically. We go on to analyze the mathematical system on multiple timescales. First, we consider a long timescale where tumor evasion is likely due to adaptive (and somewhat deterministic) immuno-editing. Then, we consider the temporal mesoscale and hypothesize that extrinsic noise could be a major factor in induction of immuno-evasion. Implications of immuno-evasive mechanisms for the outcome of immunotherapies are also discussed. In addition, we discuss the ideas that population level tumor dormancy may not be a quiescence phenomenon and that dormant tumors can, at least if modulated by the immune system, live a very active and noisy life!
  Advances in experimental medicine and biology 01/2013; 734:111-143.
• Article: Livin' with NCX and Lovin' It: A 45 Year Romance.

  Mordecai P Blaustein
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  ABSTRACT: This conference commemorates, almost to the day, the 45th anniversary of the discovery of the Na(+)/Ca(2+) exchanger (NCX). The discovery was serendipitous, as is so often the case with scientific breakthroughs. Indeed, that is what is so fascinating and romantic about scientific research. I will describe the discovery of NCX, but will begin by explaining how I got there, and will then discuss how the discovery influenced my career path.
  Advances in experimental medicine and biology 01/2013; 961:3-15.
• Article: Gawky (GW) is the Drosophila melanogaster GW182 Homologue.

  Jing Li, Tom C Hobman, Andrew J Simmonds
  Advances in experimental medicine and biology 01/2013; 768:127-45.
• Article: CD133(+) Cells for the Treatment of Degenerative Diseases: Update and Perspectives.

  Mirella Meregalli, Andrea Farini, Marzia Belicchi, Yvan Torrente
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  ABSTRACT: Stem cells are used in cell therapy for degenerative disorders. The main advantage of stem cells is that they can replenish their numbers for long periods through cell division and produce a progeny that can differentiate into multiple cell lineages with specific functions. CD133 is a member of a novel family of cell surface glycoproteins. The expression of human CD133 (AC133 antigen) was originally described in the hematopoietic CD34(+) stem cells, but now it becomes more and more evident that CD133 is a marker of stem and progenitor cell populations originating from various tissues and organs. The main objective of this chapter is to describe the potential sources of CD133(+) stem cells that harbor the ability to engraft, proliferate, and differentiate into functional cells. The characterization of such CD133(+) stem cells unlocks new opportunities in the treatment of degenerative diseases such as Duchenne muscular dystrophy.
  Advances in experimental medicine and biology 01/2013; 777:229-43.
• Article: Acute effects of physical exercise on prefrontal cortex activity in older adults: a functional near-infrared spectroscopy study.

  Takeo Tsujii, Kazutoshi Komatsu, Kaoru Sakatani
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  ABSTRACT: We examined the acute effect of physical exercise on prefrontal cortex activity in older adults using functional near-infrared spectroscopy (NIRS). Fourteen older adults visited our laboratory twice: once for exercise and once for the control condition. On each visit, subjects performed working memory tasks before and after moderate intensity exercise with a cycling ergo-meter. We measured the NIRS response at the prefrontal cortex during the working memory task. We found that physical exercise improved behavioral performance of the working memory task compared with the control condition. Moreover, NIRS analysis showed that physical exercise enhanced the prefrontal cortex activity, especially in the left hemisphere, during the working memory task. These findings suggest that the moderate intensity exercise enhanced the prefrontal cortex activity associated with working memory performance in older adults.
  Advances in experimental medicine and biology 01/2013; 765:293-8.
• Article: DNA methyltransferases, DNA damage repair, and cancer.

  Bilian Jin, Keith D Robertson
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  ABSTRACT: The maintenance DNA methyltransferase (DNMT) 1 and the de novo methyltransferases DNMT3A and DNMT3B are all essential for mammalian development. DNA methylation, catalyzed by the DNMTs, plays an important role in maintaining genome stability. Aberrant expression of DNMTs and disruption of DNA methylation patterns are closely associated with many forms of cancer, although the exact mechanisms underlying this link remain elusive. DNA damage repair systems have evolved to act as a genome-wide surveillance mechanism to maintain chromosome integrity by recognizing and repairing both exogenous and endogenous DNA insults. Impairment of these systems gives rise to mutations and directly contributes to tumorigenesis. Evidence is mounting for a direct link between DNMTs, DNA methylation, and DNA damage repair systems, which provide new insight into the development of cancer. Like tumor suppressor genes, an array of DNA repair genes frequently sustain promoter hypermethylation in a variety of tumors. In addition, DNMT1, but not the DNMT3s, appear to function coordinately with DNA damage repair pathways to protect cells from sustaining mutagenic events, which is very likely through a DNA methylation-independent mechanism. This chapter is focused on reviewing the links between DNA methylation and the DNA damage response.
  Advances in experimental medicine and biology 01/2013; 754:3-29.
• Article: Physiological control of germline development.

  E Jane Albert Hubbard, Dorota Z Korta, Diana Dalfó
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  ABSTRACT: The intersection between developmental programs and environmental conditions that alter physiology is a growing area of research interest. The C. elegans germ line is emerging as a particularly sensitive and powerful model for these studies. The germ line is subject to environmentally regulated diapause points that allow worms to withstand harsh conditions both prior to and after reproduction commences. It also responds to more subtle changes in physiological conditions. Recent studies demonstrate that different aspects of germ line development are sensitive to environmental and physiological changes and that conserved signaling pathways such as the AMPK, Insulin/IGF, TGFβ, and TOR-S6K, and nuclear hormone receptor pathways mediate this sensitivity. Some of these pathways genetically interact with but appear distinct from previously characterized mechanisms of germline cell fate control such as Notch signaling. Here, we review several aspects of hermaphrodite germline development in the context of "feasting," "food-limited," and "fasting" conditions. We also consider connections between lifespan, metabolism and the germ line, and we comment on special considerations for examining germline development under altered environmental and physiological conditions. Finally, we summarize the major outstanding questions in the field.
  Advances in experimental medicine and biology 01/2013; 757:101-31.
• Article: Introduction to purinergic signalling in the brain.

  Geoffrey Burnstock
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  ABSTRACT: ATP is a cotransmitter with glutamate, noradrenaline, GABA, acetylcholine and dopamine in the brain. There is a widespread presence of both adenosine (P1) and P2 nucleotide receptors in the brain on both neurons and glial cells. Adenosine receptors play a major role in presynaptic neuromodulation, while P2X ionotropic receptors are involved in fast synaptic transmission and synaptic plasticity. P2Y G protein-coupled receptors are largely involved in presynaptic activities, as well as mediating long-term (trophic) signalling in cell proliferation, differentiation and death during development and regeneration. Both P1 and P2 receptors participate in neuron-glial interactions. Purinergic signalling is involved in control of cerebral vascular tone and remodelling and has been implicated in learning and memory, locomotor and feeding behaviour and sleep. There is increasing interest in the involvement of purinergic signalling in the pathophysiology of the CNS, including trauma, ischaemia, epilepsy, neurodegenerative diseases, neuropsychiatric and mood disorders, and cancer, including gliomas.
  Advances in experimental medicine and biology 01/2013; 986:1-12.
• Article: Function of GW182 and GW Bodies in siRNA and miRNA Pathways.

  Bing Yao, Songqing Li, Edward K L Chan
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  ABSTRACT: GW182 is an 182 kDa protein with multiple glycine/tryptophan repeats (GW or WG) playing a central role in siRNA- and miRNA-mediated gene silencing. GW182 interacts with its functional partner Argonaute proteins (AGO) via multiple domains to exert its silencing activity in both pathways. In siRNA-mediated silencing, knockdown either GW182 or Ago2 causes loss of silencing activity correlating with the disassembly of GWBs. In contrast, GW182 and its longer isoform TNGW1 appear to be downstream repressors that function independent of Ago2, whereas the Ago2-GW182 interaction is critical for the localization of Ago2 in the cytoplasmic foci and its repression function. GW182 contains two non-overlapping repression domains that can trigger translational repression with mild effect on mRNA decay. Collectively, GW182 plays a critical role in miRNA-mediated gene silencing.
  Advances in experimental medicine and biology 01/2013; 768:71-96.
• Article: Relationship of GW/P-Bodies with Stress Granules.

  Georg Stoecklin, Nancy Kedersha
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  ABSTRACT: Whereas P-bodies are intimately linked to the cytoplasmic RNA decay machinery, stress granules harbor stalled translation initiation complexes that accumulate upon stress-induced translation arrest. In this Chapter, we reflect on the relationship between P-bodies and stress granules. In mammalian cells, the two structures can be clearly distinguished from each other using specific protein or RNA markers, but they also share many proteins and mRNAs. While the formation of P-bodies and stress granules is coordinately triggered by stress, their assembly appears to be regulated independently by different pathways. Under certain types of stress, P-bodies frequently dock with stress granules, and overexpressing certain proteins that localize to both structures can cause P-body/stress granule fusion. Currently available data suggest that these self-assembling compartments are controlled by flux of mRNAs within the cytoplasm, and that their assembly mirrors the translation and degradation rates of their component mRNAs.
  Advances in experimental medicine and biology 01/2013; 768:197-211.
• Article: Helicases at the replication fork.

  Peter McGlynn
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  ABSTRACT: Helicases are fundamental components of all replication complexes since unwinding of the double-stranded template to generate single-stranded DNA is essential to direct DNA synthesis by polymerases. However, helicases are also required in many other steps of DNA replication. Replicative helicases not only unwind the template DNA but also play key roles in regulating priming of DNA synthesis and coordination of leading and lagging strand DNA polymerases. Accessory helicases also aid replicative helicases in unwinding of the template strands in the presence of proteins bound to the DNA, minimising the risks posed by nucleoprotein complexes to continued fork movement. Helicases also play critical roles in Okazaki fragment processing in eukaryotes and may also be needed to minimise topological problems when replication forks converge. Thus fork movement, coordination of DNA synthesis, lagging strand maturation and termination of replication all depend on helicases. Moreover, if disaster strikes and a replication fork breaks down then reloading of the replication machinery is effected by helicases, at least in bacteria. This chapter describes how helicases function in these multiple steps at the fork and how DNA unwinding is coordinated with other catalytic processes to ensure efficient, high fidelity duplication of the genetic material in all organisms.
  Advances in experimental medicine and biology 01/2013; 767:97-121.