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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/28938617/development-and-validation-of-nomogram-based-on-lncrna-zfas1-for-predicting-survival-in-lymph-node-negative-esophageal-squamous-cell-carcinoma-patients
#2
Hongtai Shi, Zhenhua Liu, Dong Pei, Youqin Jiang, Haiwen Zhu, Bin Chen
BACKGROUND: There is increasing evidence of a relationship between long non-coding RNA (lncRNA) and cancer. This study aimed to examine the prognostic value of the lncRNA ZFAS1 in esophageal squamous cell carcinoma (ESCC). RESULTS: The results showed that ZFAS1 expression was significantly higher in ESCC tissues compared with the corresponding adjacent normal tissues (P < 0.001). ESCC patients with high ZFAS1 expression had a poor overall survival (OS). Histological grade, T stage and ZFAS1 expression were integrated to develop the nomogram...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938533/trans-sialidase-based-vaccine-candidate-protects-against-trypanosoma-cruzi-infection-not-only-inducing-an-effector-immune-response-but-also-affecting-cells-with-regulatory-suppressor-phenotype
#3
Estefanía Prochetto, Carolina Roldán, Iván A Bontempi, Daiana Bertona, Luz Peverengo, Miguel H Vicco, Luz M Rodeles, Ana R Pérez, Iván S Marcipar, Gabriel Cabrera
Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control. Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938530/cd3xpdl1-bi-specific-t-cell-engager-bite-simultaneously-activates-t-cells-and-nkt-cells-kills-pdl1-tumor-cells-and-extends-the-survival-of-tumor-bearing-humanized-mice
#4
Lucas A Horn, Nicholas G Ciavattone, Ryan Atkinson, Netsanet Woldergerima, Julia Wolf, Virginia K Clements, Pratima Sinha, Munanchu Poudel, Suzanne Ostrand-Rosenberg
Bi-specific T cell engagers (BiTEs) activate T cells through CD3 and target activated T cells to tumor-expressed antigens. BiTEs have shown therapeutic efficacy in patients with liquid tumors; however, they do not benefit all patients. Anti-tumor immunity is limited by Programmed Death 1 (PD1) pathway-mediated immune suppression, and patients who do not benefit from existing BiTES may be non-responders because their T cells are anergized via the PD1 pathway. We have designed a BiTE that activates and targets both T cells and NKT cells to PDL1(+) cells...
August 29, 2017: Oncotarget
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
#5
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/28938014/intestinal-helminth-infection-drives-carcinogenesis-in-colitis-associated-colon-cancer
#6
Eva Pastille, Annika Frede, Henry J McSorley, Jessica Gräb, Alexandra Adamczyk, Sebastian Kollenda, Wiebke Hansen, Matthias Epple, Jan Buer, Rick M Maizels, Robert Klopfleisch, Astrid M Westendorf
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs). This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation...
September 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28938005/recombinant-vaccines-of-a-cd4-t-cell-epitope-promote-efficient-control-of-paracoccidioides-brasiliensis-burden-by-restraining-primary-organ-infection
#7
Rodrigo Assunção Holanda, Julián Esteban Muñoz, Lucas Santos Dias, Leandro Buffoni Roque Silva, Julliana Ribeiro Alves Santos, Sthefany Pagliari, Érica Leandro Marciano Vieira, Tatiane Alves Paixão, Carlos Pelleschi Taborda, Daniel Assis Santos, Oscar Bruña-Romero
Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay...
September 22, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28937975/umbilical-cord-blood-cells-for-treatment-of-cerebral-palsy-timing-and-treatment-options
#8
REVIEW
Courtney A McDonald, Michael C Fahey, Graham Jenkin, Suzanne L Miller
Cerebral palsy is the most common cause of physical disability in children, and there is no cure. Umbilical cord blood (UCB) cell therapy for the treatment of children with cerebral palsy is currently being assessed in clinical trials. While there is much interest in the use of UCB stem cells for neuroprotection and neuroregeneration, the mechanisms of action are not fully understood. Further, UCB contains many stem and progenitor cells of interest, and we will point out that individual cell types within UCB may elicit specific effects...
September 22, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28937691/toward-a-conceptual-framework-for-early-brain-and-behavior-development-in-autism
#9
J Piven, J T Elison, M J Zylka
Studies of infant siblings of older autistic probands, who are at elevated risk for autism, have demonstrated that the defining features of autism are not present in the first year of life but emerge late in the first and into the second year. A recent longitudinal neuroimaging study of high-risk siblings revealed a specific pattern of brain development in infants later diagnosed with autism, characterized by cortical surface area hyper-expansion in the first year followed by brain volume overgrowth in the second year that is associated with the emergence of autistic social deficits...
October 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28937634/the-physiological-and-pathological-implications-of-the-formation-of-hydrogels-with-a-specific-focus-on-amyloid-polypeptides
#10
REVIEW
Létitia Jean, Alex C Foley, David J T Vaux
Hydrogels are water-swollen and viscoelastic three-dimensional cross-linked polymeric network originating from monomer polymerisation. Hydrogel-forming polypeptides are widely found in nature and, at a cellular and organismal level, they provide a wide range of functions for the organism making them. Amyloid structures, arising from polypeptide aggregation, can be damaging or beneficial to different types of organisms. Although the best-known amyloids are those associated with human pathologies, this underlying structure is commonly used by higher eukaryotes to maintain normal cellular activities, and also by microbial communities to promote their survival and growth...
September 22, 2017: Biomolecules
https://www.readbyqxmd.com/read/28937406/tolerance-in-xenotransplantation
#11
Kazuhiko Yamada, Megan Sykes, David H Sachs
PURPOSE OF REVIEW: This review describes recent progress in tolerance-inducing strategies across xenogeneic immunological barriers as well as the potential benefit of a tolerance strategy for islets and kidney xenotransplantation. RECENT FINDINGS: Using advanced gene editing technologies, xenotransplantation from multitransgenic alpha-1,3-galactosyltransferase knockout pigs has demonstrated marked prolongation of renal xenograft survival, ranging from days to greater than several months for life-supporting kidneys, and more than 2 years in a heterotopic nonlife-supporting cardiac xenograft model...
September 20, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28936781/coordinate-expression-of-pan-neuronal-and-functional-signature-genes-in-sympathetic-neurons
#12
U Ernsberger, M Kramer, K Tsarovina, T Deller, H Rohrer
Neuron subtypes of the mature nervous system differ in the expression of characteristic marker genes while they share the expression of generic neuronal genes. The regulatory logic that maintains subtype-specific and pan-neuronal genes is not well understood. To begin to address this issue, we analyze RNA sequencing results from whole sympathetic ganglia and single sympathetic neurons in the mouse. We focus on gene products involved in the neuronal cytoskeleton, neurotransmitter synthesis and storage, transmitter release and reception and electrical information processing...
September 21, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28936621/expression-of-inflammatory-lipopolysaccharide-binding-protein-lbp-predicts-the-progression-of-conventional-renal-cell-carcinoma-a-short-report
#13
Gyula Kovacs, Lehel Peterfi, Nelli Farkas, Andras Javorhazy, Csaba Pusztai, Arpad Szanto
BACKGROUND: The mortality of conventional renal cell carcinoma (RCC) correlates directly with the presence or postoperative development of metastases. The aim of this study was to identify new markers associated with the postoperative progression of conventional RCC. METHODS: Tissue microarrays (TMA) of conventional RCC from a cohort of 414 patients were analysed by immunohistochemistry for expression of the lipopolysaccharide binding protein (LBP), which was identified as a candidate biomarker through Affymetrix U133 Plus 2...
September 21, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28936523/mesoporous-zno-nanocapsules-for-the-induction-of-enhanced-antigen-specific-immunological-responses
#14
Sumbul Afroz, Himadri Medhi, Somedutta Maity, Gillipsie Minhas, Srikanth Battu, Jeevan Giddaluru, Koushi Kumar, Pradip Paik, Nooruddin Khan
The application of nanotechnology in vaccinology has fuelled rapid advancement towards the design and development of nanovaccines. Nanoparticles have been found to enhance vaccine efficacy through the spatiotemporal orchestration of antigen delivery to secondary lymphoid organs and antigen-presentation by Antigen Presenting Cells (APCs) synchronized with stimulation of innate and adaptive immune responses. Metal based nanoparticles (MNPs) have been extensively engineered for the generation of nanovaccines owing to their intrinsic adjuvant-like properties and immunomodulatory functions...
September 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28936485/a-randomized-controlled-trial-of-lisinopril-to-decrease-lymphoid-fibrosis-in-antiretroviral-treated-hiv-infected-individuals
#15
Leslie R Cockerham, Steven A Yukl, Kara Harvill, Ma Somsouk, Sunil K Joshi, Elizabeth Sinclair, Teri Liegler, Rebecca Hoh, Sophie Lyons, Peter W Hunt, Adam Rupert, Irini Sereti, David R Morcock, Ajantha Rhodes, Claire Emson, Marc K Hellerstein, Jacob D Estes, Sharon Lewin, Steven G Deeks, Hiroyu Hatano
BACKGROUND: In HIV infection, lymphoid tissue is disrupted by fibrosis. Angiotensin converting enzyme inhibitors have anti-fibrotic properties. We completed a pilot study to assess whether the addition of lisinopril to antiretroviral therapy (ART) reverses fibrosis of gut tissue, and whether this leads to reduction of HIV RNA and DNA levels. METHODS: Thirty HIV-infected individuals on ART were randomized to lisinopril at 20mg daily or matching placebo for 24 weeks...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28935958/differential-regulation-of-effector-and-regulatory-t-cell-function-by-blimp1
#16
Rashmi Bankoti, Chihiro Ogawa, Truc Nguyen, Lena Emadi, Michael Couse, Soofia Salehi, Xuemo Fan, Deepti Dhall, Yizhou Wang, Jordan Brown, Vincent Funari, Jie Tang, Gislâine A Martins
The transcriptional regulator Blimp1 plays crucial roles in controlling terminal differentiation in several lineages. In T cells, Blimp1 is expressed in both effector (Teff) and regulatory (Treg) cells, and mice with T cell-specific deletion of Blimp1 (Blimp1CKO mice) spontaneously develop severe intestinal inflammation, indicating a crucial role for Blimp1 in T cell homeostasis regulation. Blimp1 has been shown to function as a direct activator of the Il10 gene and although its requirement for IL10 expression has been demonstrated in both Treg and Teff cells under inflammatory conditions, the intrinsic requirement of Blimp1 for homeostatic maintenance of these T cell subsets had not been investigated...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935940/layer-and-cell-type-selective-co-transmission-by-a-basal-forebrain-cholinergic-projection-to-the-olfactory-bulb
#17
Daniel T Case, Shawn D Burton, Jeremy Y Gedeon, Sean-Paul G Williams, Nathaniel N Urban, Rebecca P Seal
Cholinergic neurons in the basal forebrain project heavily to the main olfactory bulb, the first processing station in the olfactory pathway. The projections innervate multiple layers of the main olfactory bulb and strongly influence odor discrimination, detection, and learning. The precise underlying circuitry of this cholinergic input to the main olfactory bulb remains unclear, however. Here, we identify a specific basal forebrain cholinergic projection that innervates select neurons concentrated in the internal plexiform layer of the main olfactory bulb...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28935938/an-engineered-bispecific-dna-encoded-igg-antibody-protects-against-pseudomonas-aeruginosa-in-a-pneumonia-challenge-model
#18
Ami Patel, Antonio DiGiandomenico, Ashley E Keller, Trevor R F Smith, Daniel H Park, Stephanie Ramos, Katherine Schultheis, Sarah T C Elliott, Janess Mendoza, Kate E Broderick, Megan C Wise, Jian Yan, Jingjing Jiang, Seleeke Flingai, Amir S Khan, Kar Muthumani, Laurent Humeau, Lily I Cheng, Leslie Wachter-Rosati, C Kendall Stover, Niranjan Y Sardesai, David B Weiner
The impact of broad-spectrum antibiotics on antimicrobial resistance and disruption of the beneficial microbiome compels the urgent investigation of bacteria-specific approaches such as antibody-based strategies. Among these, DNA-delivered monoclonal antibodies (DMAbs), produced by muscle cells in vivo, potentially allow the prevention or treatment of bacterial infections circumventing some of the hurdles of protein IgG delivery. Here, we optimize DNA-delivered monoclonal antibodies consisting of two potent human IgG clones, including a non-natural bispecific IgG1 candidate, targeting Pseudomonas aeruginosa...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28935714/profiling-mhc-ii-immunopeptidome-of-blood-stage-malaria-reveals-that-cdc1-control-the-functionality-of-parasite-specific-cd4-t-cells
#19
Marion Draheim, Myriam F Wlodarczyk, Karine Crozat, Jean-Michel Saliou, Tchilabalo Dilezitoko Alayi, Stanislas Tomavo, Ali Hassan, Anna Salvioni, Claudia Demarta-Gatsi, John Sidney, Alessandro Sette, Marc Dalod, Antoine Berry, Olivier Silvie, Nicolas Blanchard
In malaria, CD4 Th1 and T follicular helper (TFH) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins...
September 21, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28935708/unraveling-transcriptome-dynamics-in-human-spermatogenesis
#20
S Z Jan, T L Vormer, A Jongejan, M Röling, S J Silber, D G de Rooij, G Hamer, S Repping, A M M van Pelt
Spermatogenesis is a dynamic developmental process that includes stem cell proliferation and differentiation, meiotic cell divisions and extreme chromatin condensation. Although studied in mice, the molecular control of human spermatogenesis is largely unknown. Here, we developed a protocol that enables next generation sequencing of RNA obtained from pools of 500 individually laser capture microdissected cells of specific germ cell-subtypes from fixed human testis samples. Transcriptomic analyses of these successive germ cell subtypes reveals dynamic transcription of over 4000 genes during human spermatogenesis...
September 21, 2017: Development
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