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https://www.readbyqxmd.com/read/28650342/inflammatory-ly6chi-monocytes-and-their-conversion-to-m2-macrophages-drive-atherosclerosis-regression
#1
Karishma Rahman, Yuliya Vengrenyuk, Stephen A Ramsey, Noemi Rotllan Vila, Natasha M Girgis, Jianhua Liu, Viktoria Gusarova, Jesper Gromada, Ada Weinstock, Kathryn J Moore, P'ng Loke, Edward A Fisher
Atherosclerosis is a chronic inflammatory disease, and developing therapies to promote its regression is an important clinical goal. We previously established that atherosclerosis regression is characterized by an overall decrease in plaque macrophages and enrichment in markers of alternatively activated M2 macrophages. We have now investigated the origin and functional requirement for M2 macrophages in regression in normolipidemic mice that received transplants of atherosclerotic aortic segments. We compared plaque regression in WT normolipidemic recipients and those deficient in chemokine receptors necessary to recruit inflammatory Ly6Chi (Ccr2-/- or Cx3cr1-/-) or patrolling Ly6Clo (Ccr5-/-) monocytes...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28642583/sox2-is-required-for-inner-ear-neurogenesis
#2
Aleta R Steevens, Danielle L Sookiasian, Jenna C Glatzer, Amy E Kiernan
Neurons of the cochleovestibular ganglion (CVG) transmit hearing and balance information to the brain. During development, a select population of early otic progenitors express NEUROG1, delaminate from the otocyst, and coalesce to form the neurons that innervate all inner ear sensory regions. At present, the selection process that determines which otic progenitors activate NEUROG1 and adopt a neuroblast fate is incompletely understood. The transcription factor SOX2 has been implicated in otic neurogenesis, but its requirement in the specification of the CVG neurons has not been established...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642276/dedifferentiation-proliferation-and-redifferentiation-of-adult-mammalian-cardiomyocytes-after-ischemic-injury
#3
Wei Eric Wang, Liangpeng Li, Xuewei Xia, Wenbin Fu, Qiao Liao, Cong Lan, Dezhong Yang, Hongmei Chen, Rongchuan Yue, Cindy S Zeng, Lin Zhou, Bin Zhou, Dayue D Duan, Xiongwen Chen, Steven R Houser, Chunyu Zeng
Background -Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACM) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. Methods -β-actin-GFP transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs...
June 22, 2017: Circulation
https://www.readbyqxmd.com/read/28636400/click-biotinylation-of-plga-template-for-biotin-receptor-oriented-delivery-of-doxorubicin-hydrochloride-in-4t1-cell-induced-breast-cancer
#4
Yuvraj Singh, K K Durga Rao Viswanadham, Arun Kumar Jajoriya, Jayagopal Meher, Kavit Raval, Swati Jaiswal, Jayant Dewangan, H K Bora, Srikanta Kumar Rath, Jawahar Lal, Durga Prasad Mishra, Manish Kumar Chourasia
PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (Biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However adequate entrapment of a hydrophilic bioactive like DOX in a hydrophobic polymer system made of PLGA is not usually possible. We therefore modified a conventional W/O/W emulsion method by utilizing ammonium chloride in the external phase to constrain DOX in dissolved polymer phase by supressing its inherent aqueous solubility as per common ion effect...
June 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28631093/myelin-regulatory-factor-drives-remyelination-in-multiple-sclerosis
#5
Greg J Duncan, Jason R Plemel, Peggy Assinck, Sohrab B Manesh, Fraser G W Muir, Ryan Hirata, Matan Berson, Jie Liu, Michael Wegner, Ben Emery, G R Wayne Moore, Wolfram Tetzlaff
Remyelination is limited in the majority of multiple sclerosis (MS) lesions despite the presence of oligodendrocyte precursor cells (OPCs) in most lesions. This observation has led to the view that a failure of OPCs to fully differentiate underlies remyelination failure. OPC differentiation requires intricate transcriptional regulation, which may be disrupted in chronic MS lesions. The expression of few transcription factors has been differentially compared between remyelinating lesions and lesions refractory to remyelination...
June 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28621414/micrornas-in-drosophila-regulate-cell-fate-by-repressing-single-mrna-targets
#6
Noam Perry, Marina Volin, Hila Toledano
Regulation of gene expression governs all aspects of the lifespan of the organism, such as embryonic development, stem cell differentiation, reproduction and aging. Among the most important regulators of these extremely complex processes are microRNAs (miRNAs), small non-coding RNAs that repress gene expression by binding to primary sequences on the mRNA of their target. Theoretically, the mere existence of a miRNA recognition sequence on a given mRNA is sufficient to generate a functional response. Since these short sequences are abundant, one miRNA can potentially bind to multiple targets, thus generating endless possible biological outcomes...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28619821/convergence-of-signaling-pathways-underlying-habenular-formation-and-axonal-outgrowth
#7
Sara Roberson, Marnie E Halpern
The habenular nuclei are a conserved integrating center in the vertebrate epithalamus where they modulate diverse behaviors. Despite their importance, our understanding of habenular development is incomplete. Time-lapse imaging and fate mapping demonstrate that the dorsal habenulae (dHb) of zebrafish are derived from dbx1b-expressing (dbx1b(+)) progenitors, which transition into cxcr4b-expressing neuronal precursors. The precursors give rise to differentiated neurons whose axons innervate the midbrain interpeduncular nucleus (IPN)...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28611151/fate-mapping-neurons-and-glia-derived-from-dbx1-expressing-progenitors-in-mouse-preb%C3%A3-tzinger-complex
#8
Andrew Kottick, Caroline A Martin, Christopher A Del Negro
The brainstem preBötzinger complex (preBötC) generates the inspiratory breathing rhythm, and its core rhythmogenic interneurons are derived from Dbx1-expressing progenitors. To study the neural bases of breathing, tamoxifen-inducible Cre-driver mice and Cre-dependent reporters are used to identify, record, and perturb Dbx1 preBötC neurons. However, the relationship between tamoxifen administration and reporter protein expression in preBötC neurons and glia has not been quantified. To address this problem, we crossed mice that express tamoxifen-inducible Cre recombinase under the control of the Dbx1 gene (Dbx1(Cre)(ERT)(2)) with Cre-dependent fluorescent reporter mice (Rosa26(tdTomato)), administered tamoxifen at different times during development, and analyzed tdTomato expression in the preBötC of their offspring...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28606987/the-fate-and-lifespan-of-human-monocyte-subsets-in-steady-state-and-systemic-inflammation
#9
Amit A Patel, Yan Zhang, James N Fullerton, Lies Boelen, Anthony Rongvaux, Alexander A Maini, Venetia Bigley, Richard A Flavell, Derek W Gilroy, Becca Asquith, Derek Macallan, Simon Yona
In humans, the monocyte pool comprises three subsets (classical, intermediate, and nonclassical) that circulate in dynamic equilibrium. The kinetics underlying their generation, differentiation, and disappearance are critical to understanding both steady-state homeostasis and inflammatory responses. Here, using human in vivo deuterium labeling, we demonstrate that classical monocytes emerge first from marrow, after a postmitotic interval of 1.6 d, and circulate for a day. Subsequent labeling of intermediate and nonclassical monocytes is consistent with a model of sequential transition...
June 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28606934/cell-lineage-of-timed-cohorts-of-tbx6-expressing-cells-in-wild-type-and-tbx6-mutant-embryos
#10
Daniel Concepcion, Andrew J Washkowitz, Akiko DeSantis, Phillip Ogea, Jason I Yang, Nataki C Douglas, Virginia E Papaioannou
Tbx6 is a T-box transcription factor with multiple roles in embryonic development as evidenced by dramatic effects on mesoderm cell fate determination, left/right axis determination, and somite segmentation in mutant mice. The expression of Tbx6 is restricted to the primitive streak and presomitic mesoderm, but some of the phenotypic features of mutants are not easily explained by this expression pattern. We have used genetically-inducible fate mapping to trace the fate of Tbx6-expressing cells in wild type and mutant embryos to explain some of the puzzling features of the mutant phenotype...
June 12, 2017: Biology Open
https://www.readbyqxmd.com/read/28604738/emt-cells-increase-breast-cancer-metastasis-via-paracrine-gli-activation-in-neighbouring-tumour-cells
#11
Deepika Neelakantan, Hengbo Zhou, Michael U J Oliphant, Xiaomei Zhang, Lukas M Simon, David M Henke, Chad A Shaw, Meng-Fen Wu, Susan G Hilsenbeck, Lisa D White, Michael T Lewis, Heide L Ford
Recent fate-mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that these studies failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumour cells in a paracrine manner, in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits growth in PDX models...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28589361/the-aid-cre-ert2-model-a-tool-for-monitoring-b-cell-immune-responses-and-generating-selective-hybridomas
#12
Simon Le Gallou, Takuya Nojima, Daisuke Kitamura, Jean-Claude Weill, Claude-Agnès Reynaud
Expression of activation-induced cytidine deaminase (AID) is the hallmark of B cells engaged in an immune response in germinal centers. We designed an inducible fate-mapping reporter mouse in which AID-expressing B cells could be timely and irreversibly marked, by knockin at the Aicda locus of a tamoxifen-inducible Cre recombinase. This mouse model allows notably for the long-term follow-up of memory B cells and plasma cells engaged in an immune response. We describe here a protocol to generate hybridomas from small memory subsets that can be easily traced and identified in this mouse line through Cre-activated fluorescent reporters...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28589347/fate-mapping-and-transcript-profiling-of-germinal-center-cells-by-two-photon-photoconversion
#13
Imogen Moran, Tri Giang Phan
The germinal center (GC) reaction is the key process for the generation of high affinity antibodies to foreign antigen. Standard experimental techniques such as fluorescence-activated cell sorting and histology have provided numerous insights into the composition and function of the GC. However, these approaches are limited to a "snapshot" in time and are unable to fully capture the dynamic nature of the GC. Intravital two-photon microscopy overcomes these disadvantages and has led to several major advances in the field but is restricted by practical and technical limits that prevent long-range mapping and molecular studies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28584128/bcl11b-and-combinatorial-resolution-of-cell-fate-in-the-t-cell-gene-regulatory-network
#14
William J R Longabaugh, Weihua Zeng, Jingli A Zhang, Hiroyuki Hosokawa, Camden S Jansen, Long Li, Maile Romero-Wolf, Pentao Liu, Hao Yuan Kueh, Ali Mortazavi, Ellen V Rothenberg
T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28584126/temperature-variability-is-integrated-by-a-spatially-embedded-decision-making-center-to-break-dormancy-in-arabidopsis-seeds
#15
Alexander T Topham, Rachel E Taylor, Dawei Yan, Eiji Nambara, Iain G Johnston, George W Bassel
Plants perceive and integrate information from the environment to time critical transitions in their life cycle. Some mechanisms underlying this quantitative signal processing have been described, whereas others await discovery. Seeds have evolved a mechanism to integrate environmental information by regulating the abundance of the antagonistically acting hormones abscisic acid (ABA) and gibberellin (GA). Here, we show that hormone metabolic interactions and their feedbacks are sufficient to create a bistable developmental fate switch in Arabidopsis seeds...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28576641/a-quantitative-study-of-the-intracellular-fate-of-ph-responsive-doxorubicin-polypeptide-nanoparticles
#16
Jing Wang, Jayanta Bhattacharyya, Eric Mastria, Ashutosh Chilkoti
Nanoscale carriers with an acid-labile linker between the carrier and drug are commonly used for drug delivery. However, their efficacy is potentially limited by inefficient linker cleavage, and lysosomal entrapment of drugs. To address these critical issues, we developed a new imaging method that spatially overlays the location of a nanoparticle and the released drug from the nanoparticle, on a map of the local intracellular pH that delineates individual endosomes and lysosomes, and the therapeutic intracellular target of the drug-the nucleus...
May 30, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28573750/chondrification-and-character-identification-in-the-skull-exemplified-for-the-basicranial-anatomy-of-early-squamate-embryos
#17
Oleksandr Yaryhin, Ingmar Werneburg
The neurocranium of vertebrates is mainly derived from early cartilaginous anlagen, the so-called chondrocranium, the base of the future skull. Two initial bar-shaped and paired chondrifications flank the notochord, the rostral trabecles and the caudal parachordals. In most reptiles, there is an additional component, the transverse acrochordal, which is placed between trabecles and parachordals. All these elements compose the base of the future chondrocranium. There are several drastically different hypotheses concerning the development and interrelationship of these elements...
June 1, 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/28569405/sex-dependent-osteoblast-stage-specific-effects-of-progesterone-receptor-on-bone-acquisition
#18
Zhendong A Zhong, Alexander Kot, Yu-An E Lay, Hongliang Zhang, Junjing Jia, Nancy E Lane, Wei Yao
The role of the progesterone receptor (PR) in the regulation of sexual dimorphism in bone has yet to be determined. Here we utilized genetic fate mapping and western blotting to demonstrate age-dependent PR expression in the mouse femoral metaphysis and diaphysis. To define sex-dependent and osteoblast stage-specific effects of PR on bone acquisition, we selectively deleted PR at different stages of osteoblast differentiation. We found that when Prx1-Cre mice were crossed with PR floxed mice to generate a MSC conditional KO model (Prx1; PRcKO), the mutant mice developed greater trabecular bone volume with higher mineral apposition rate and bone formation...
June 1, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28559476/noncanonical-alternative-polyadenylation-contributes-to-gene-regulation-in-response-to-hypoxia
#19
Laura de Lorenzo, Reed Sorenson, Julia Bailey-Serres, Arthur G Hunt
Stresses from various environmental challenges continually confront plants, and their responses are important for growth and survival. One molecular response to such challenges involves the alternative polyadenylation of mRNA. In plants, it is unclear how stress affects the production and fate of alternative mRNA isoforms. Using a genome-scale approach, we show that in Arabidopsis thaliana, hypoxia leads to increases in the number of mRNA isoforms with polyadenylated 3' ends that map to 5'-UTRs, introns and protein-coding regions...
May 30, 2017: Plant Cell
https://www.readbyqxmd.com/read/28554399/transplantation-of-reprogrammed-neurons-for-improved-recovery-after-stroke
#20
Zaal Kokaia, Daniel Tornero, Olle Lindvall
Somatic cells such as fibroblasts, reprogrammed to induced pluripotent stem cells, can be used to generate neural stem/progenitor cells or neuroblasts for transplantation. In this review, we summarize recent studies demonstrating that when grafted intracerebrally in animal models of stroke, reprogrammed neurons improve function, probably by several different mechanisms, e.g., trophic actions, modulation of inflammation, promotion of angiogenesis, cellular and synaptic plasticity, and neuroprotection. In our own work, we have shown that human skin-derived reprogrammed neurons, fated to cortical progeny, integrate in stroke-injured neuronal network and form functional afferent synapses with host neurons, responding to peripheral sensory stimulation...
2017: Progress in Brain Research
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