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https://www.readbyqxmd.com/read/28938749/the-testicular-transcriptome-associated-with-spermatogonia-differentiation-initiated-by-gonadotrophin-stimulation-in-the-juvenile-rhesus-monkey-macaca-mulatta
#1
Suresh Ramaswamy, William H Walker, Paula Aliberti, Rahil Sethi, Gary R Marshall, Alyxzandria Smith, Seyedmehdi Nourashrafeddin, Alicia Belgorosky, Uma R Chandran, Mark P Hedger, Tony M Plant
STUDY QUESTION: What is the genetic landscape within the testis of the juvenile rhesus monkey (Macaca mulatta) that underlies the decision of undifferentiated spermatogonia to commit to a pathway of differentiation when puberty is induced prematurely by exogenous LH and FSH stimulation? SUMMARY ANSWER: Forty-eight hours of gonadotrophin stimulation of the juvenile monkey testis resulted in the appearance of differentiating B spermatogonia and the emergence of 1362 up-regulated and 225 down-regulated testicular mRNAs encoding a complex network of proteins ranging from enzymes regulating Leydig cell steroidogenesis to membrane receptors, and from juxtacrine and paracrine factors to transcriptional factors governing spermatogonial stem cell fate...
October 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28938423/igfbp4-is-required-for-adipogenesis-and-influences-the-distribution-of-adipose-depots
#2
David E Maridas, Victoria E DeMambro, Phuong T Le, Subburaman Mohan, Clifford J Rosen
Insulin-like Growth Factor I (IGF-I) induces adipogenesis in vitro. IGF Binding Protein 4 (IGFBP4) is highly expressed in adipocytes and osteoblasts and is inhibitory of IGFs in vitro. We previously reported that Igfbp4 null mice (Igfbp4-/-) had decreased fat proportions at 8 and 16 weeks of age. However, the mechanism leading to the reduced adiposity remains unknown. The purpose of this study was to elucidate how IGFBP4 mediates adipose tissue development in vivo. Our results showed that inguinal (iWAT) and gonadal (gWAT) white adipose tissues from Igfbp4-/- mice had decreased weights and Pparγ expression...
July 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938163/tumor-cell-targeted-delivery-of-crispr-cas9-by-aptamer-functionalized-lipopolymer-for-therapeutic-genome-editing-of-vegfa-in-osteosarcoma
#3
Chao Liang, Fangfei Li, Luyao Wang, Zong-Kang Zhang, Chao Wang, Bing He, Jie Li, Zhihao Chen, Atik Badshah Shaikh, Jin Liu, Xiaohao Wu, Songlin Peng, Lei Dang, Baosheng Guo, Xiaojuan He, D W T Au, Cheng Lu, Hailong Zhu, Bao-Ting Zhang, Aiping Lu, Ge Zhang
Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment...
September 13, 2017: Biomaterials
https://www.readbyqxmd.com/read/28937614/a-novel-vav3-homolog-identified-in-lamprey-lampetra-japonica-with-roles-in-lipopolysaccharide-mediated-immune-response
#4
Yanqi Shen, Yishan Zhang, Yinglun Han, Peng Su, Meng Gou, Yue Pang, Qingwei Li, Xin Liu
Vav guanine nucleotide exchange factor 3 (Vav3), a Rho family GTPase, regulates multiple cell signaling pathways including those of T- and B-cell receptors in vertebrates through mediating the activities of the Rho family members. Whether the lamprey possesses Vav3 homolog and what role it plays in immune response remain unknown. Gene cloning, recombinant expression, antibody production and expression pattern analyses were performed to characterize the lamprey Vav3 in the current study. The lamprey Vav3 is closer to jawed vertebrates' Vav3 molecules (about 53% identities in general) than to Vav2 molecules of jawless and jawed vertebrates (about 51% identities in general) in sequence similarity...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28936869/ratiometric-fluorescence-sensor-for-the-microrna-determination-by-catalyzed-hairpin-assembly
#5
Yi Liu, Tian Shen, Jing Li, Hang Gong, Chunyan Chen, Xiaoming Chen, Changqun Cai
A novel catalyzed hairpin assembly-based turn-on ratiometric fluorescence biosensor was constructed for the determination of microRNA-122 (miRNA-122) by using 2-aminopurine (2-AP) and thioflavin T (ThT) as detection signal sources. Hairpin DNA sequence (H1) includes the complementary strands of miRNA-122 and G-quadruplex-forming sequence. When miRNA-122 was presented, hybridization occurred between miRNA-122 and part of H1, causing a double-stranded DNA and a G-quadruplex formed. The formed double-stranded DNA significantly decreased the fluorescence intensity of 2-AP...
September 22, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28936210/novel-mutations-of-the-tetratricopeptide-repeat-domain-7a-gene-and-phenotype-genotype-comparison
#6
Reyin Lien, Yung-Feng Lin, Min-Wei Lai, Hui-Ying Weng, Ren-Chin Wu, Tang-Her Jaing, Jing-Long Huang, Shih-Feng Tsai, Wen-I Lee
The gastrointestinal tract contains the largest lymphoid organ to react with pathogenic microorganisms and suppress excess inflammation. Patients with primary immunodeficiency diseases (PIDs) can suffer from refractory diarrhea. In this study, we present two siblings who began to suffer from refractory diarrhea with a poor response to aggressive antibiotic and immunosuppressive treatment after surgical release of neonatal intestinal obstruction. Their lymphocyte proliferation was low, but superoxide production and IL-10 signaling were normal...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935569/constitutive-cd40-signaling-in-dendritic-cells-limits-atherosclerosis-by-provoking-inflammatory-bowel-disease-and-ensuing-cholesterol-malabsorption
#7
Pascal Kusters, Tom Seijkens, Christina Bürger, Bart Legein, Holger Winkels, Marion Gijbels, Christian Barthels, Remy Bennett, Linda Beckers, Dorothee Atzler, Erik Biessen, Thomas Brocker, Christian Weber, Norbert Gerdes, Esther Lutgens
The co-stimulatory molecule CD40 is a major driver of atherosclerosis. It is expressed on a wide variety of cell types including mature dendritic cells (DCs) and is required for optimal T cell activation and expansion. It remains undetermined if and how CD40 on DCs impacts the pathogenesis of atherosclerosis. Here we examined the effects of constitutively active CD40 in DCs on atherosclerosis, using low-density lipoprotein-deficient (Ldlr(-/-)) bone-marrow chimeras that express a transgene containing an engineered latent membrane protein 1 (LMP)/CD40 fusion protein conferring constitutive CD40 signaling under control of the DC-specific CD11c promoter (DC-LMP1/CD40)...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28935506/endothelial-specific-sirt3-deletion-impairs-glycolysis-and-angiogenesis-and-causes-diastolic-dysfunction
#8
Xiaochen He, Heng Zeng, Sean T Chen, Richard J Roman, Judy L Aschner, Sean Didion, Jian-Xiong Chen
Endothelial glycolysis plays a critical role in the regulation of angiogenesis. We investigated the role of Sirtuin 3 (SIRT3) on endothelial cell (EC) glycolytic metabolism, angiogenesis, and diastolic function. Our aim was to test the hypothesis that loss of SIRT3 in ECs impairs endothelial glycolytic metabolism and angiogenesis and contributes to myocardial capillary rarefaction and the development of diastolic dysfunction. Using SIRT3 deficient ECs, SIRT3 was found to regulate a metabolic switch between mitochondrial respiration and glycolysis...
September 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28935500/mold-metabolites-drive-rheumatoid-arthritis-in-mice-via-promotion-of-ifn-gamma-and-il-17-producing-t-cells
#9
Susanne Jahreis, Stephanie Kuhn, Anna-Maria Madaj, Mario Bauer, Tobias Polte
Environmental factors have been discussed as triggers for autoimmune diseases like rheumatoid arthritis (RA). However, the role of chemical exposures in activation or exacerbation of RA is not clarified yet. Exposure of DBA/1 mice to the mold metabolites ochratoxin A (OTA) or deoxynivalenol (DON) increased the prevalence and the clinical severity of RA compared to un-exposed mice using an experimental collagen-induced arthritis model. Mycotoxin-exposed mice showed enhanced serum IgG1 and IgG2a levels and an elevated production of IL-1β and IL-6 in inflamed joints and of IFN-γ and IL-17 in splenocytes...
September 18, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28935478/development-and-validation-of-a-cell-based-assay-for-the-detection-of-neutralizing-antibodies-against-recombinant-insulins
#10
Sanjukta Chatterjee, Laxmikant Vashishta, Vinit S Waichale, Vivek G Nayak, Ramakrishnan Melarkode, Charles M Donnelly, Patrick T Vallano, Narendra Chirmule, Nilanjan Sengupta
Recombinant biopharmaceuticals can induce generation of anti-drug antibodies, which could potentially neutralize therapeutic drug activity. In this report, we describe development and validation of a cell-based assay for detection of neutralizing antibodies (Nab) against insulin and insulin analogues. In order to achieve clinically meaningful sensitivity the method used an early signalling event, insulin induced insulin receptor phosphorylation as the endpoint. Percentage insulin receptor phosphorylation in cell lysates was measured using ECL based ELISA...
September 18, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28934393/neurofibromatosis-type-1-alternative-splicing-is-a-key-regulator-of-ras-erk-signaling-and-learning-behaviors-in-mice
#11
Hieu T Nguyen, Melissa N Hinman, Xuan Guo, Alok Sharma, Hiroyuki Arakawa, Guangbin Luo, Hua Lou
Appropriate activation of the Ras/extracellular signal-regulated kinase (ERK) protein signaling cascade within the brain is crucial for optimal learning and memory. One key regulator of this cascade is the Nf1 Ras GTPase activating protein (RasGAP), which attenuates Ras/ERK signaling by converting active Ras is bound to guanosine triphosphate, activating Ras into inactive Ras is bound to guanosine diphosphate, inactivating Ras. A previous study using embryonic stem cells and embryonic stem cell-derived neurons indicated that Nf1 RasGAP activity is modulated by the highly regulated alternative splicing of Nf1 exon 23a...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934122/invasion-of-dendritic-cells-macrophages-and-neutrophils-by-the-bordetella-adenylate-cyclase-toxin-a-subversive-move-to-fool-host-immunity
#12
REVIEW
Giorgio Fedele, Ilaria Schiavoni, Irena Adkins, Nela Klimova, Peter Sebo
Adenylate cyclase toxin (CyaA) is released in the course of B. pertussis infection in the host's respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC), macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3',5'-cyclic adenosine monophosphate (cAMP), which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells...
September 21, 2017: Toxins
https://www.readbyqxmd.com/read/28934113/sphingosine-1-phosphate-signaling-and-its-pharmacological-modulation-in-allogeneic-hematopoietic-stem-cell-transplantation
#13
REVIEW
Philip Smith, Catherine O'Sullivan, Peter Gergely
Allogeneic haemopoietic stem cell transplantation (HSCT) is increasingly used to treat haematological malignant diseases via the graft-versus-leukaemia (GvL) or graft-versus-tumour effects. Although improvements in infectious disease prophylaxis, immunosuppressive treatments, supportive care, and molecular based tissue typing have contributed to enhanced outcomes, acute graft-versus-host disease and other transplant related complications still contribute to high mortality and significantly limit the more widespread use of HSCT...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28933920/multi-tissue-transcriptomics-delineates-the-diversity-of-airway-t-cell-functions-in-asthma
#14
Akul Singhania, Joshua C Wallington, Caroline G Smith, Daniel Horowitz, Karl J Staples, Peter H Howarth, Stephan D Gadola, Ratko Djukanović, Christopher H Woelk, Timothy Sc Hinks
Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma, and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3+ T cells from sputum and bronchoalveolar lavage were obtained from healthy subjects (N=19) and asthmatic patients (mild, moderate and severe asthma; N=46). Gene expression was assessed using Affymetrix HT HG-U133+ PM GeneChips and results were validated by real-time quantitative PCR...
September 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28932817/designing-biomaterials-with-immunomodulatory-properties-for-tissue-engineering-and-regenerative-medicine
#15
REVIEW
James I Andorko, Christopher M Jewell
Recent research in the vaccine and immunotherapy fields has revealed that biomaterials have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. Intriguingly, new studies reveal these responses are influenced by the physicochemical properties of the material. Nearly all of this work has been done in the vaccine and immunotherapy fields, but there is tremendous opportunity to apply this same knowledge to tissue engineering and regenerative medicine. This review discusses recent findings that reveal how material properties-size, shape, chemical functionality-impact immune response, and links these changes to emerging opportunities in tissue engineering and regenerative medicine...
June 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/28932637/muc1-c-promotes-the-suppressive-immune-microenvironment-in-non-small-cell-lung-cancer
#16
Audrey Bouillez, Dennis Adeegbe, Caining Jin, Xiufeng Hu, Ashujit Tagde, Maroof Alam, Hasan Rajabi, Kwok-Kin Wong, Donald Kufe
The cancer immune microenvironment is of importance for the effectiveness of immunotherapy; however, its dysregulation is poorly understood. The MUC1-C oncoprotein is aberrantly overexpressed in non-small cell lung cancer (NSCLC) and has been linked to the induction of PD-L1. The present work investigated the effects of targeting MUC1-C in an immuno-competent MUC1 transgenic (MUC1.Tg) mouse model. We show that Lewis Lung Carcinoma cells expressing MUC1-C (LLC/MUC1) exhibit upregulation of PD-L1 and suppression of interferon-γ (IFN-γ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932225/expression-and-function-of-the-cholinergic-system-in-immune-cells
#17
REVIEW
Takeshi Fujii, Masato Mashimo, Yasuhiro Moriwaki, Hidemi Misawa, Shiro Ono, Kazuhide Horiguchi, Koichiro Kawashima
T and B cells express most cholinergic system components-e.g., acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase, and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Using ChAT(BAC)-eGFP transgenic mice, ChAT expression has been confirmed in T and B cells, dendritic cells, and macrophages. Moreover, T cell activation via T-cell receptor/CD3-mediated pathways upregulates ChAT mRNA expression and ACh synthesis, suggesting that this lymphocytic cholinergic system contributes to the regulation of immune function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28931944/errant-gardeners-glial-cell-dependent-synaptic-pruning-and-neurodevelopmental-disorders
#18
REVIEW
Urte Neniskyte, Cornelius T Gross
The final stage of brain development is associated with the generation and maturation of neuronal synapses. However, the same period is also associated with a peak in synapse elimination - a process known as synaptic pruning - that has been proposed to be crucial for the maturation of remaining synaptic connections. Recent studies have pointed to a key role for glial cells in synaptic pruning in various parts of the nervous system and have identified a set of critical signalling pathways between glia and neurons...
September 21, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28931816/tgf%C3%AE-r-signalling-controls-cd103-cd11b-dendritic-cell-development-in-the-intestine
#19
C C Bain, J Montgomery, C L Scott, J M Kel, M J H Girard-Madoux, L Martens, T F P Zangerle-Murray, J Ober-Blöbaum, D Lindenbergh-Kortleve, J N Samsom, S Henri, T Lawrence, Y Saeys, B Malissen, M Dalod, B E Clausen, A McI Mowat
CD103(+)CD11b(+) dendritic cells (DCs) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGFβR1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103(+)CD11b(+) DCs and a reciprocal increase in the CD103(-)CD11b(+) dendritic cell subset. Transcriptional profiling identifies markers that define the CD103(+)CD11b(+) DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103(+)CD11b(+) DCs in CD11c-Cre...
September 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28931676/protective-humoral-immunity-in-the-cns-requires-peripheral-cd19-dependent-germinal-center-formation-following-coronavirus-encephalomyelitis
#20
Jeffrey R Atkinson, Cornelia C Bergmann
B cell subsets with phenotypes characteristic of naïve, non-isotype-switched, memory (Bmem), and antibody-secreting cells (ASC) accumulate in various models of central nervous system (CNS) inflammation, including viral encephalomyelitis. During neurotropic coronavirus JHMV infection infiltration of protective ASC occurs after T cell mediated viral control, and is preceded by accumulation of non-isotype switched IgD(+) and IgM(+) B cells. However, the contribution of peripheral activation events in cervical lymph nodes (CLN) in driving humoral immune responses in the infected CNS is poorly defined...
September 20, 2017: Journal of Virology
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