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https://www.readbyqxmd.com/read/28228010/selective-fusion-of-heterogeneous-classifiers-for-predicting-substrates-of-membrane-transporters
#1
Naeem Shaikh, Mahesh Sharma, Prabha Garg
Membrane transporters play a crucial role in determining fate of administered drugs in a biological system. Early identification of plausible transporters for a drug molecule can provide insights into its therapeutic, pharmacokinetic and toxicological profile. In the present study, predictive models for classifying small molecules into substrates and non-substrates of various pharmaceutically important membrane transporters are developed using QSAR and proteochemometric (PCM) approaches. For this purpose, 4575 substrate interactions for these transporters were collected from Metabolism and Transport Database (Metrabase) and literature...
February 23, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28209809/macrophage-to-myofibroblast-transition-contributes-to-interstitial-fibrosis-in-chronic-renal-allograft-injury
#2
Ying-Ying Wang, Hong Jiang, Jun Pan, Xiao-Ru Huang, Yu-Cheng Wang, Hong-Feng Huang, Ka-Fai To, David J Nikolic-Paterson, Hui-Yao Lan, Jiang-Hua Chen
Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α-smooth muscle actin [α-SMA]) markers...
February 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28209733/dual-function-of-tgf%C3%AE-in-lens-epithelial-cell-fate-implications-for-secondary-cataract
#3
Bruce A Boswell, Anna Korol, Judith A West-Mays, Linda S Musil
The most common vision-disrupting complication of cataract surgery is posterior capsule opacification (PCO; secondary cataract). PCO is caused by residual lens cells undergoing one of two very different cell fates: either transdifferentiating into myofibroblasts, or maturing into lens fiber cells. Although TGFβ has been strongly implicated in lens cell fibrosis, the factors responsible for the latter process have not been identified. We show here for the first time that TGFβ can induce purified primary lens epithelial cells within the same culture to undergo differentiation into either lens fiber cells or myofibroblasts...
February 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28192080/evo-engineering-and-the-cellular-and-molecular-origins-of-the-vertebrate-spinal-cord
#4
REVIEW
Ben Steventon, Alfonso Martinez Arias
The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specific spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posteriorly localized signalling source transforms previously anterior-specified neural plate into the spinal cord...
February 9, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28177282/cilia-mediated-hedgehog-signaling-controls-form-and-function-in-the-mammalian-larynx
#5
Jacqueline M Tabler, Maggie M Rigney, Gordon J Berman, Swetha Gopalakrishnan, Eglantine Heude, Hadeel A Al-Lami, Basil Z Yannakoudakis, Rebecca D Fitch, Christopher M Carter, Steven A Vokes, Karen J Liu, Shahragim Tajbakhsh, Se Roian Egnor, John B Wallingford
Acoustic communication is fundamental to social interactions among animals, including humans. In fact, deficits in voice impair the quality of life for a large and diverse population of patients. Understanding the molecular genetic mechanisms of development and function in the vocal apparatus is thus an important challenge with relevance both to the basic biology of animal communication and to biomedicine. However, surprisingly little is known about the developmental biology of the mammalian larynx. Here, we used genetic fate mapping to chart the embryological origins of the tissues in the mouse larynx, and we describe the developmental etiology of laryngeal defects in mice with disruptions in cilia-mediated Hedgehog signaling...
February 8, 2017: ELife
https://www.readbyqxmd.com/read/28174244/a-novel-floor-plate-boundary-defined-by-adjacent-en1-and-dbx1-microdomains-distinguishes-midbrain-dopamine-and-hypothalamic-neurons
#6
Navid Nouri, Rajeshwar Awatramani
The mesodiencephalic floor plate (mdFP) is the source of diverse neuron types. Yet, how this structure is compartmentalized has not been clearly elucidated. Here, we identify a novel boundary subdividing the mdFP into two microdomains, defined by Engrailed 1 (En1) and developing brain homeobox 1 (Dbx1) Utilizing simultaneous dual and intersectional fate mapping, we demonstrate that this boundary is precisely formed with minimal overlap between En1 and Dbx1 microdomains, unlike many other boundaries. We show that the En1 microdomain gives rise to dopaminergic (DA) neurons, while the Dbx1 microdomain gives rise to subthalamic (STN), premammillary (PM), and posterior hypothalamic (PH) populations...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28143982/differential-binding-of-mitochondrial-transcripts-by-mrb8170-and-mrb4160-regulates-distinct-editing-fates-of-mitochondrial-mrna-in-trypanosomes
#7
Sameer Dixit, Michaela Müller-McNicoll, Vojtěch David, Kathi Zarnack, Jernej Ule, Hassan Hashimi, Julius Lukeš
: A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitochondrion of Trypanosoma brucei Several protein complexes have been implicated in performing this type of RNA editing, including the mitochondrial RNA-binding complex 1 (MRB1). Two paralogous novel RNA-binding proteins, MRB8170 and MRB4160, are loosely associated with the core MRB1 complex. Their roles in RNA editing and effects on target mRNAs are so far not well understood. In this study, individual-nucleotide-resolution UV-cross-linking and affinity purification (iCLAP) revealed a preferential binding of both proteins to mitochondrial mRNAs, which was positively correlated with their extent of editing...
January 31, 2017: MBio
https://www.readbyqxmd.com/read/28139650/corrigendum-clonal-fate-mapping-quantifies-the-number-of-haematopoietic-stem-cells-that-arise-during-development
#8
Jonathan Henninger, Buyung Santoso, Stefan Hans, Ellen Durand, Jessica Moore, Christian Mosimann, Michael Brand, David Traver, Leonard Zon
No abstract text is available yet for this article.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28135253/alternative-pathway-for-the-development-of-v%C3%AE-14-nkt-cells-directly-from-cd4-cd8-thymocytes-that-bypasses-the-cd4-cd8-stage
#9
Nyambayar Dashtsoodol, Tomokuni Shigeura, Minako Aihara, Ritsuko Ozawa, Satoshi Kojo, Michishige Harada, Takaho A Endo, Takashi Watanabe, Osamu Ohara, Masaru Taniguchi
Although invariant Vα14(+) natural killer T cells (NKT cells) are thought to be generated from CD4(+)CD8(+) double-positive (DP) thymocytes, the developmental origin of CD4(-)CD8(-) double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (TH1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage...
March 2017: Nature Immunology
https://www.readbyqxmd.com/read/28133805/evolution-of-b-cell-analysis-and-env-trimer-redesign
#10
REVIEW
Gunilla B Karlsson Hedestam, Javier Guenaga, Martin Corcoran, Richard T Wyatt
HIV-1 and its surface envelope glycoproteins (Env), gp120 and gp41, have evolved immune evasion strategies that render the elicitation of effective antibody responses to the functional Env entry unit extremely difficult. HIV-1 establishes chronic infection and stimulates vigorous immune responses in the human host; forcing selection of viral variants that escape cellular and antibody (Ab)-mediated immune pressure, yet possess contemporary fitness. Successful survival of fit variants through the gauntlet of the human immune system make this virus and these glycoproteins a formidable challenge to target by vaccination, requiring a systematic approach to Env mimetic immunogen design and evaluation of elicited responses...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28125268/multipotent-myoepithelial-progenitor-cells-are-born-early-during-airway-submucosal-gland-development
#11
Preston J Anderson, Thomas J Lynch, John F Engelhardt
Airway submucosal glands (SMGs) are facultative stem cell niches for the surface epithelium, but the phenotype of the SMG-derived progenitor cells remains unclear. In other organs, glandular myoepithelial cells (MECs) have been proposed to be multipotent progenitors for luminal cells. We sought to determine the developmental phase during which mouse tracheal glandular MECs are born and whether these MECs are progenitors for other cell phenotypes during SMG morphogenesis. To approach this question, we localized two MEC protein markers (α-smooth muscle actin [αSMA/ACTA2] and smooth muscle myosin heavy chain 11 [SMMHC/MYH11]) during various stages of SMG development (placode, elongation, branching, and differentiation) and used ACTA2-CreERT2 and MYH11-CreERT2 transgenic mice to fate map MEC-derived lineages during SMG morphogenesis...
January 26, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28122327/dual-roles-for-regulatory-t-cell-depletion-and-co-stimulatory-signaling-in-agonistic-gitr-targeting-for-tumor-immunotherapy
#12
Ashley Mahne, Smita Mauze, Barbara Joyce-Shaikh, Jane Xia, Edward Bowman, Amy Beebe, Daniel Cua, Renu Jain
Agonistic monoclonal antibodies (mAb) targeting the T cell receptor co-regulatory molecule GITR exert potent therapeutic activities in preclinical tumor models. Although anti-GITR mAb are thought to act by depleting and destabilizing the intratumoral T regulatory cell (Treg) population, the precise mechanism of action is obscure. Here we addressed this issue using a Treg fate-mapping approach, which revealed that Treg loss was primarily due to cell depletion, with minimal evidence of Treg conversion to a non-Foxp3-expressing population...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/28118409/epigenetic-landscape-of-kaposi-s-sarcoma-associated-herpesvirus-genome-in-classic-kaposi-s-sarcoma-tissues
#13
Rui Sun, Xiaohua Tan, Xing Wang, Xiaodong Wang, Lei Yang, Erle S Robertson, Ke Lan
Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically related to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). It typically displays two different phases in its life cycle, the default latency and occasional lytic replication. The epigenetic modifications are thought to determine the fate of KSHV infection. Previous studies elegantly depicted epigenetic landscape of latent viral genome in in vitro cell culture systems. However, the physiologically relevant scenario in clinical KS tissue samples is unclear...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28117356/ependymal-cell-contribution-to-scar-formation-after-spinal-cord-injury-is-minimal-local-and-dependent-on-direct-ependymal-injury
#14
Yilong Ren, Yan Ao, Timothy M O'Shea, Joshua E Burda, Alexander M Bernstein, Andrew J Brumm, Nagendran Muthusamy, H Troy Ghashghaei, S Thomas Carmichael, Liming Cheng, Michael V Sofroniew
Ependyma have been proposed as adult neural stem cells that provide the majority of newly proliferated scar-forming astrocytes that protect tissue and function after spinal cord injury (SCI). This proposal was based on small, midline stab SCI. Here, we tested the generality of this proposal by using a genetic knock-in cell fate mapping strategy in different murine SCI models. After large crush injuries across the entire spinal cord, ependyma-derived progeny remained local, did not migrate and contributed few cells of any kind and less than 2%, if any, of the total newly proliferated and molecularly confirmed scar-forming astrocytes...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28116490/comprehensive-and-accurate-tracking-of-carbon-origin-of-lc-tandem-mass-spectrometry-collisional-fragments-for-13-c-mfa
#15
Jannick Kappelmann, Bianca Klein, Petra Geilenkirchen, Stephan Noack
In recent years the benefit of measuring positionally resolved (13)C-labeling enrichment from tandem mass spectrometry (MS/MS) collisional fragments for improved precision of (13)C-Metabolic Flux Analysis ((13)C-MFA) has become evident. However, the usage of positional labeling information for (13)C-MFA faces two challenges: (1) The mass spectrometric acquisition of a large number of potentially interfering mass transitions may hamper accuracy and sensitivity. (2) The positional identity of carbon atoms of product ions needs to be known...
January 23, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28109470/the-fate-of-the-free-flap-pedicle-after-free-tissue-transfer-to-the-head-and-neck-area
#16
Maarten L V Van Genechten, Martin D Batstone
OBJECTIVES: Little is understood about what happens to the vascular pedicle following free tissue transfer in the head and neck region. The viability of a free flap completely depends on the vascular supply by its vascular pedicle until neovascularization occurs from surrounding tissues. The aim of this study is to find out how long a vascular pedicle lasts following free tissue transfer in the head and neck region. MATERIALS AND METHODS: Patients were recruited from the Maxillofacial Unit at the Royal Brisbane & Women's Hospital...
February 2017: Oral Oncology
https://www.readbyqxmd.com/read/28107664/safety-and-efficacy-of-cardiopoietic-stem-cells-in-the-treatment-of-post-infarction-left-ventricular-dysfunction-from-cardioprotection-to-functional-repair-in-a-translational-pig-infarction-model
#17
Maximilian Y Emmert, Petra Wolint, Andras Jakab, Sean P Sheehy, Francesco S Pasqualini, Thi Dan Linh Nguyen, Monika Hilbe, Burkhardt Seifert, Benedikt Weber, Chad E Brokopp, Dominika Macejovska, Etem Caliskan, Arnold von Eckardstein, Ruth Schwartlander, Viola Vogel, Volkmar Falk, Kevin Kit Parker, Mariann Gyöngyösi, Simon P Hoerstrup
To date, clinical success of cardiac cell-therapies remains limited. To enhance the cardioreparative properties of stem cells, the concept of lineage-specification through cardiopoietic-guidance has been recently suggested. However, so far, only results from murine studies and from a clinical pilot-trial in chronic heart-failure (CHF) are available, while systematic evidence of its therapeutic-efficacy is still lacking. Importantly, also no data from large animals or for other indications are available. Therefore, we here investigate the therapeutic-efficacy of human cardiopoietic stem cells in the treatment of post-infarction LV-dysfunction using a translational pig-model...
April 2017: Biomaterials
https://www.readbyqxmd.com/read/28100680/th22-cells-form-a-distinct-th-lineage-from-th17-cells-in-vitro-with-unique-transcriptional-properties-and-tbet-dependent-th1-plasticity
#18
Maximilian W Plank, Gerard E Kaiko, Steven Maltby, Jessica Weaver, Hock L Tay, Wei Shen, Mark S Wilson, Scott K Durum, Paul S Foster
Th22 cells are a major source of IL-22 and have been found at sites of infection and in a range of inflammatory diseases. However, their molecular characteristics and functional roles remain largely unknown because of our inability to generate and isolate pure populations. We developed a novel Th22 differentiation assay and generated dual IL-22/IL-17A reporter mice to isolate and compare pure populations of cultured Th22 and Th17 cells. Il17a fate-mapping and transcriptional profiling provide evidence that these Th22 cells have never expressed IL-17A, suggesting that they are potentially a distinct cell lineage from Th17 cells under in vitro culture conditions...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28095652/exosomal-trafficking-in-xenopus-development
#19
REVIEW
Michael Danilchik, Tess Tumarkin
Exosomes are small extracellular vesicles (EVs) secreted by many cell types in both normal and pathogenic circumstances. Because EVs, particularly exosomes, are known to transfer biologically active proteins, RNAs and lipids between cells, they have recently become the focus of intense interest as potential mediators of cell-cell communication, particularly in long-range and juxtacrine signaling events associated with adaptive immune function and progression of cancer. Among the EVs, exosomes appear particularly adapted for long-range delivery of cargoes between cells...
January 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28077488/id2-controls-specification-of-lgr5-intestinal-stem-cell-progenitors-during-gut-development
#20
Lira Nigmatullina, Maxim Norkin, Margarita M Dzama, Berith Messner, Sergi Sayols, Natalia Soshnikova
The adult intestinal stem cells (ISCs), their hierarchies, mechanisms of maintenance and differentiation have been extensively studied. However, when and how ISCs are established during embryogenesis remains unknown. We show here that the transcription regulator Id2 controls the specification of embryonic Lgr5(+) progenitors in the developing murine small intestine. Cell fate mapping analysis revealed that Lgr5(+) progenitors emerge at E13.5 in wild-type embryos and differ from the rest on the intestinal epithelium by a characteristic ISC signature...
January 11, 2017: EMBO Journal
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