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Trends in Molecular Medicine

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https://www.readbyqxmd.com/read/28716624/mitochondrial-aminoacyl-trna-synthetases-in-human-disease
#1
REVIEW
Marie Sissler, Ligia Elena González-Serrano, Eric Westhof
Dysfunctions in mitochondria - the powerhouses of the cell - lead to several human pathologies. Because mitochondria integrate nuclear and mitochondrial genetic systems, they are richly intertwined with cellular activities. The nucleus-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key components of the mitochondrial translation apparatus. Mutations in these enzymes predominantly affect the central nervous system (CNS) but also target other organs. Comparable mutations in mt-aaRSs can lead to vastly diverse diseases, occurring at different stages in life, and within different tissues; this represents a confounding issue...
July 14, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28697885/neutralizing-the-threat-pan-ebolavirus-antibodies-close-the-loop
#2
Chad E Mire, Thomas W Geisbert
The glycoprotein (GP) of ebolaviruses participates in a critical membrane fusion process to establish infection of a cell and therefore, represents an important target of both vaccines and antivirals. The latest reports on pan-ebolavirus monoclonal antibodies in small animal models may offer promising outcomes and insight into how best to target the GP in vaccine and antiviral discovery.
July 8, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28694141/amylin-receptor-a-potential-therapeutic-target-for-alzheimer-s-disease
#3
REVIEW
Wen Fu, Aarti Patel, Ryoichi Kimura, Rania Soudy, Jack H Jhamandas
Alzheimer'sdisease (AD) is a progressive neurodegenerative disorder, characterized by senile plaques constituting extracellular deposits of β-amyloid (Aβ) fibrils. Since Aβ accumulation in the brain is considered an early event preceding, by decades, cognitive dysfunction, disease-modifying treatments are aimed at facilitating clearance of this protein from the brain or ameliorating its toxic effects. Recent studies have identified the amylin receptor as a capable mediator of the deleterious actions of Aβ and furthermore, administration of amylin receptor-based peptides has been shown to improve spatial memory and learning in transgenic mouse models of AD...
July 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28694140/mirnas-in-b-cell-development-and-lymphomagenesis
#4
REVIEW
Maryaline Coffre, Sergei B Koralov
B lymphocytes are essential for an efficient immune response against a variety of pathogens. A large fraction of hematologic malignancies is of B cell origin, suggesting that the development and activation of B cells need to be tightly regulated. In recent years, increasing evidence has emerged demonstrating that microRNAs (miRNAs) - a class of non-coding RNAs that control gene expression - are involved in the regulation of B cell development and function. We provide here an overview of the current knowledge on the role of miRNAs and their relevant targets in B cell development, B cell activation, and B cell malignant transformation...
July 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28576602/biomarkers-of-human-pluripotent-stem-cell-derived-cardiac-lineages
#5
REVIEW
Rhys J P Skelton, Timothy J Kamp, David A Elliott, Reza Ardehali
Human pluripotent stem cells (hPSCs) offer a practical source for the de novo generation of cardiac tissues and a unique opportunity to investigate cardiovascular lineage commitment. Numerous strategies have focused on the in vitro production of cardiomyocytes, smooth muscle, and endothelium from hPSCs. However, these differentiation protocols often yield undesired cell types. Thus, establishing a set of stage-specific markers for pure cardiac subpopulations will assist in defining the hierarchy of cardiac differentiation, aid in the development of cellular therapy, and facilitate drug screening and disease modeling...
May 30, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28576601/linc-ing-the-noncoding-genome-to-heart-function-beating-hypertrophy
#6
Shambhabi Chatterjee, Christian Bär, Thomas Thum
The principal event of aberrant gene expression occurs in numerous disorders and syndromes, including heart failure. LncRNAs may constitute powerful treatment targets because they intensively interact with their genetic environment, as they are important regulators of genetic networks. Recent advances on the functional roles of lncRNAs in cardiac hypertrophy are expected to usher improved therapeutic strategies.
May 30, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28648962/exosomes-as-reconfigurable-therapeutic-systems
#7
REVIEW
R Steven Conlan, Simone Pisano, Marta I Oliveira, Mauro Ferrari, I Mendes Pinto
Historically, small molecules, including steroid hormones and cytokines, have been attributed a role in paracrine and endocrine signaling, and now include a new player: biological nanoparticles, or 'exosomes'. Generated intracellularly, and defined simply as nanoparticulate packages of signaling moieties, exosomes have emerged as vehicles for highly specialized local and distant intercellular communication. Exosomes are increasingly being recognized as contributing factors in many diseases, and their potential as biomarkers and in therapeutics is rapidly emerging...
May 29, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28648961/uterine-fluid-in-pregnancy-a-biological-and-clinical-outlook
#8
REVIEW
Ying Zhang, Qiang Wang, Hongmei Wang, Enkui Duan
Once considered a simple medium for sperm and embryo transport, the functional spectrum of uterine fluid is now expanding. Novel molecular players, such as extracellular vesicles and mobile RNAs, have been detected in the uterine fluid of livestock, rodents, and humans. These novel molecules, together with previously known ions and proteins, ensure uterine fluid homeostasis and facilitate embryo-maternal interactions. Here, we propose that these molecules may also carry information that mirrors maternal environmental exposure and possibly relay such information to the embryo via uterine fluid, generating long-term epigenetic effects on the offspring via embryonic and placental programming...
May 25, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28499701/should-we-stop-saying-glia-and-neuroinflammation
#9
REVIEW
Roser Masgrau, Carmen Guaza, Richard M Ransohoff, Elena Galea
Central nervous system (CNS) therapeutics based on the theoretical framework of neuroinflammation have only barely succeeded. We argue that a problem may be the wrong use of the term 'neuroinflammation' as a distinct nosological entity when, based on recent evidence, it may not explain CNS disease pathology. Indeed, the terms 'neuroinflammation' and 'glia' could be obsolete. First, unbiased molecular profiling of CNS cell populations and individual cells reveals striking phenotypic heterogeneity in health and disease...
May 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28478951/a-crispr-approach-to-neurodegenerative-diseases
#10
Martin Kampmann
A major barrier to developing effective therapies for neurodegenerative diseases is our incomplete understanding of the underlying cellular mechanisms. Genetic screens in human-induced pluripotent stem cell-derived neurons can elucidate such mechanisms. Genome-wide screens using CRISPR interference and CRISPR activation provide complementary biological insights and may reveal potential therapeutic targets.
May 4, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28648185/exosomes-as-reconfigurable-therapeutic-systems
#11
REVIEW
R Steven Conlan, Simone Pisano, Marta I Oliveira, Mauro Ferrari, I Mendes Pinto
Historically, small molecules, including steroid hormones and cytokines, have been attributed a role in paracrine and endocrine signaling, and now include a new player: biological nanoparticles, or 'exosomes'. Generated intracellularly, and defined simply as nanoparticulate packages of signaling moieties, exosomes have emerged as vehicles for highly specialized local and distant intercellular communication. Exosomes are increasingly being recognized as contributing factors in many diseases, and their potential as biomarkers and in therapeutics is rapidly emerging...
July 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28648184/uterine-fluid-in-pregnancy-a-biological-and-clinical-outlook
#12
REVIEW
Ying Zhang, Qiang Wang, Hongmei Wang, Enkui Duan
Once considered a simple medium for sperm and embryo transport, the functional spectrum of uterine fluid is now expanding. Novel molecular players, such as extracellular vesicles and mobile RNAs, have been detected in the uterine fluid of livestock, rodents, and humans. These novel molecules, together with previously known ions and proteins, ensure uterine fluid homeostasis and facilitate embryo-maternal interactions. Here, we propose that these molecules may also carry information that mirrors maternal environmental exposure and possibly relay such information to the embryo via uterine fluid, generating long-term epigenetic effects on the offspring via embryonic and placental programming...
July 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28623084/pathogenesis-of-human-systemic-lupus-erythematosus-a-cellular-perspective
#13
REVIEW
Vaishali R Moulton, Abel Suarez-Fueyo, Esra Meidan, Hao Li, Masayuki Mizui, George C Tsokos
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. A complex interaction of genetics, environment, and hormones leads to immune dysregulation and breakdown of tolerance to self-antigens, resulting in autoantibody production, inflammation, and destruction of end-organs. Emerging evidence on the role of these factors has increased our knowledge of this complex disease, guiding therapeutic strategies and identifying putative biomarkers. Recent findings include the characterization of genetic/epigenetic factors linked to SLE, as well as cellular effectors...
July 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28587830/early-detection-of-cancer-in-blood-using-single-cell-analysis-a-proposal
#14
REVIEW
Alexander Krasnitz, Jude Kendall, Joan Alexander, Dan Levy, Michael Wigler
Here, we explore the potential of single-cell genomic analysis in blood for early detection of cancer; we consider a method that screens the presence of recurrent patterns of copy number (CN) alterations using sparse single-cell sequencing. We argue for feasibility, based on in silico analysis of existing single-cell data and cancer CN profiles. Sampling procedures from existing diploid single cells can render data for a cell with any given profile. Sampling from multiple published tumor profiles can interrogate cancer clonality via an algorithm that tests the multiplicity of close pairwise similarities among single-cell cancer genomes...
July 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28583420/the-boosting-potential-of-bacteria-in-cancer-immunotherapy
#15
David C Binder, Derek A Wainwright
Salmonella Typhimurium, engineered to express flagellin B, recently demonstrated unprecedented tumor control through a TLR-dependent mechanism. Here, we review new observations that support the potential of utilizing modified bacteria to enhance antitumor immunity. We also discuss the implications of these findings for clinical applications, including immune checkpoint blockade therapies.
July 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28571832/de-novo-gene-expression-reconstruction-in-space
#16
REVIEW
Je H Lee
The biological function of a gene often depends on spatial context, and an atlas of transcriptional regulation could be instrumental in defining functional elements across the genome. Despite recent advances in single-cell RNA sequencing and in situ RNA imaging, fundamental barriers limit the speed, genome-wide coverage, and resolution of de novo transcriptome assembly in space. Here, I discuss potential next-generation approaches for the de novo assembly of the transcriptome in space, and propose more efficient methods of detecting long-range spatial variations in gene expression...
July 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28501348/single-cell-rna-sequencing-unraveling-the-brain-one-cell-at-a-time
#17
REVIEW
Dimitry Ofengeim, Nikolaos Giagtzoglou, Dann Huh, Chengyu Zou, Junying Yuan
Single-cell RNA sequencing (scRNA-seq) is an exciting new technology allowing the analysis of transcriptomes from individual cells, and is ideally suited to address the inherent complexity and dynamics of the central nervous system. scRNA-seq has already been applied to the study of molecular taxonomy of the brain. These works have paved the way to expanding our understanding of the nervous system and provide insights into cellular susceptibilities and molecular mechanisms in neurological and neurodegenerative diseases...
June 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28483344/the-exceptional-vulnerability-of-humans-to-alzheimer-s-disease
#18
REVIEW
Lary C Walker, Mathias Jucker
Like many humans, non-human primates deposit copious misfolded Aβ protein in the brain as they age. Nevertheless, the complete behavioral and pathologic phenotype of Alzheimer's disease, including Aβ plaques, neurofibrillary (tau) tangles, and dementia, has not yet been identified in a non-human species. Recent research suggests that the crucial link between Aβ aggregation and tauopathy is somehow disengaged in aged monkeys. Understanding why Alzheimer's disease fails to develop in species that are biologically proximal to humans could disclose new therapeutic targets in the chain of events leading to neurodegeneration and dementia...
June 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28478950/emerging-role-for-methylation-in-multiple-sclerosis-beyond-dna
#19
REVIEW
Lindsay M Webb, Mireia Guerau-de-Arellano
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel tools for methylation detection or loss of function. We present evidence that MS is associated with genetic variants and metabolic changes that impact on methylation. Further, we comprehensively review current understanding of how methylation can impact on central nervous system (CNS) resilience and neuroregenerative potential, as well as inflammatory versus regulatory T helper (Th) cell balance...
June 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28461154/pathophysiology-of-tfii-i-old-guard-wearing-new-hats
#20
REVIEW
Ananda L Roy
The biochemical properties of the signal-induced multifunctional transcription factor II-I (TFII-I) indicate that it is involved in a variety of gene regulatory processes. Although gene ablation in murine models and cell-based assays show that it is encoded by an essential gene, GTF2I/Gtf2i, its physiologic role in human disorders was relatively unknown until recently. Novel studies show that it is involved in an array of human diseases including neurocognitive disorders, systemic lupus erythematosus (SLE), and cancer...
June 2017: Trends in Molecular Medicine
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