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https://www.readbyqxmd.com/read/29040995/role-of-immune-checkpoint-blockade-in-the-treatment-for-human-hepatocellular-carcinoma
#1
Naoshi Nishida, Masatoshi Kudo
With the development of molecular targeting therapy, several treatment options for advanced hepatocellular carcinoma (HCC) have become available in cases where curative and other palliative treatments, such as radiofrequency ablation, surgical resection, and transarterial chemoembolization, are not applicable. However, with the detection of a variety of mutations in cancer-related genes in a single tumor, molecular heterogeneity is commonly observed in HCC. Therefore, mutations in the major cellular signaling pathways underlie the development of resistance to molecular targeting agents...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29040950/green-spaces-are-not-all-the-same-for-the-provision-of-air-purification-and-climate-regulation-services-the-case-of-urban-parks
#2
Joana Vieira, Paula Matos, Teresa Mexia, Patrícia Silva, Nuno Lopes, Catarina Freitas, Otília Correia, Margarida Santos-Reis, Cristina Branquinho, Pedro Pinho
The growing human population concentrated in urban areas lead to the increase of road traffic and artificial areas, consequently enhancing air pollution and urban heat island effects, among others. These environmental changes affect citizen's health, causing a high number of premature deaths, with considerable social and economic costs. Nature-based solutions are essential to ameliorate those impacts in urban areas. While the mere presence of urban green spaces is pointed as an overarching solution, the relative importance of specific vegetation structure, composition and management to improve the ecosystem services of air purification and climate regulation are overlooked...
October 14, 2017: Environmental Research
https://www.readbyqxmd.com/read/29040919/functional-analyses-of-the-interaction-of-chicken-interleukin-23-subunit-p19-with-il-12-subunit-p40-to-form-the-il-23-complex
#3
Anh Duc Truong, Cong Thanh Hoang, Yeojin Hong, Janggeun Lee, Kyungbaek Lee, Hyun S Lillehoj, Yeong Ho Hong
This study represents the first description of the cloning of chicken IL-23p19 (ChIL-23α) and the function of the IL-23 complex in birds. Multiple alignment of ChIL-23α with other known IL-23α amino acid sequences revealed regions of amino acid conservation. The homologies of ChIL-23α, IL-12p35, and similar mammalian subunits ranged between 26% and 42%. ChIL-23α consisted of four exons and three introns; similar to those in humans and mice, and limited conservation of synteny between the human and chicken genomes was observed...
October 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29040885/bimodal-decompression-sickness-onset-times-are-not-related-to-dive-type-or-event-severity
#4
Amy E King, F Gregory Murphy, Laurens E Howle
Human decompression sickness (DCS) is a condition associated with depressurization during underwater diving. Human research dive trial data containing dive outcome (DCS, no-DCS) and symptom information are used to calibrate probabilistic DCS models. DCS symptom onset time information is visualized using occurrence density functions (ODF) which plot the DCS onset rate per unit time. For the BIG292 human dive trial data set, a primary U.S. Navy model calibration set, the ODFs are bimodal, however probabilistic models do not produce bimodal ODFs...
October 10, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/29040796/an-anterior-posterior-axis-within-the-ventromedial-prefrontal-cortex-separates-self-and-reward
#5
Alla Yankouskaya, Glyn Humphreys, Moritz Stolte, Mark Stokes, Zargol Moradi, Jie Sui
Although theoretical discourse and experimental studies on the self and reward biases have a long tradition, currently we have only a limited understanding of how the biases are represented in the brain and, more importantly, how they relate to each other. We used multi-voxel pattern analysis to test for common representations of self and reward in perceptual matching in healthy human subjects. Voxels across an anterior-posterior axis in ventromedial prefrontal cortex (vmPFC) distinguished (i) self-others and (ii) high-low reward, but cross generalization between these dimensions decreased from anterior to posterior vmPFC...
October 10, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/29040740/studying-developmental-psychopathology-related-to-psychotic-disorders-challenges-and-paradigms-in-human-studies
#6
Andreas Meyer-Lindenberg
No abstract text is available yet for this article.
October 10, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29040705/the-mrpp1-mrpp2-complex-is-a-trna-maturation-platform-in-human-mitochondria
#7
Linda Reinhard, Sagar Sridhara, B Martin Hällberg
Mitochondrial polycistronic transcripts are extensively processed to give rise to functional mRNAs, rRNAs and tRNAs; starting with the release of tRNA elements through 5'-processing by RNase P (MRPP1/2/3-complex) and 3'-processing by RNase Z (ELAC2). Here, we show using in vitro experiments that MRPP1/2 is not only a component of the mitochondrial RNase P but that it retains the tRNA product from the 5'-processing step and significantly enhances the efficiency of ELAC2-catalyzed 3'-processing for 17 of the 22 tRNAs encoded in the human mitochondrial genome...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040655/effects-of-1950-mhz-radiofrequency-electromagnetic-fields-on-a%C3%AE-processing-in-human-neuroblastoma-and-mouse-hippocampal-neuronal-cells
#8
Jeongyeon Park, Jong Hwa Kwon, Nam Kim, Kiwon Song
Alzheimer's disease (AD) is a neurodegenerative disease leading to progressive loss of memory and other cognitive functions. One of the well-known pathological markers of AD is the accumulation of amyloid-beta protein (Aβ), and its plaques, in the brain. Recent studies using Tg-5XFAD mice as a model of AD have reported that exposure to radiofrequency electromagnetic fields (RF-EMF) from cellular phones reduced Aβ plaques in the brain and showed beneficial effects on AD. In this study, we examined whether exposure to 1950 MHz RF-EMF affects Aβ processing in neural cells...
October 6, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/29040650/interferon-alpha-reduces-human-hippocampal-neurogenesis-and-increases-apoptosis-via-activation-of-distinct-stat1-dependent-mechanisms
#9
Alessandra Borsini, Annamaria Cattaneo, Chiara Malpighi, Sandrine Thuret, Neil A Harrison, Patricia A Zunszain, Carmine M Pariante
Background: In humans, interferon-α treatment for chronic viral hepatitis is a well-recognized clinical model for inflammation-induced depression, but the molecular mechanisms underlying these effects are not clear. Following peripheral administration in rodents, interferon-α induces signal transducer and activator of transcription-1 (STAT1) within the hippocampus and disrupts hippocampal neurogenesis. Methods: We used the human hippocampal progenitor cell line HPC0A07/03C to evaluate the effects of 2 concentrations of interferon-α, similar to those observed in human serum during its therapeutic use (500 pg/mL and 5000 pg/mL), on neurogenesis and apoptosis...
October 10, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29040648/molecular-basis-for-asymmetry-sensing-of-sirnas-by-the-drosophila-loqs-pd-dcr-2-complex-in-rna-interference
#10
Jan-Niklas Tants, Stephanie Fesser, Thomas Kern, Ralf Stehle, Arie Geerlof, Christoph Wunderlich, Michael Juen, Christoph Hartlmüller, Romy Böttcher, Stefan Kunzelmann, Oliver Lange, Christoph Kreutz, Klaus Förstemann, Michael Sattler
RNA interference defends against RNA viruses and retro-elements within an organism's genome. It is triggered by duplex siRNAs, of which one strand is selected to confer sequence-specificity to the RNA induced silencing complex (RISC). In Drosophila, Dicer-2 (Dcr-2) and the double-stranded RNA binding domain (dsRBD) protein R2D2 form the RISC loading complex (RLC) and select one strand of exogenous siRNAs according to the relative thermodynamic stability of base-pairing at either end. Through genome editing we demonstrate that Loqs-PD, the Drosophila homolog of human TAR RNA binding protein (TRBP) and a paralog of R2D2, forms an alternative RLC with Dcr-2 that is required for strand choice of endogenous siRNAs in S2 cells...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040610/the-biological-impact-of-blood-pressure-associated-genetic-variants-in-the-natriuretic-peptide-receptor-c-gene-on-human-vascular-smooth-muscle
#11
Meixia Ren, Fu Liang Ng, Helen Warren, Kate Witkowska, Michael Baron, Zhilong Jia, Claudia Cabrera, Ruoxin Zhang, Borbala Mifsud, Patricia B Munroe, Qingzhong Xiao, Andrea Townsend-Nicholson, Adrian Hobbs, Shu Ye, Mark Caulfield
Elevated blood pressure (BP) is a major global risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic variants at the NPR3 locus associated with BP, but the functional impact of these variants remains to be determined. Here we confirmed, by a genome-wide association study within UK Biobank, the existence of two independent BP-related signals within NPR3 locus. Using human primary vascular smooth muscle cells and endothelial cells from different individuals, we found that the BP-elevating alleles within one linkage disequilibrium block identified by the sentinel variant rs1173771 was associated with lower endogenous NPR3 mRNA and protein levels in vascular smooth muscle cells, together with reduced levels in open chromatin and nuclear protein binding...
October 10, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29040584/strategies-to-advance-drug-discovery-in-rare-monogenic-intellectual-disability-syndromes
#12
Nuwan C Hettige, Karla Manzano-Vargas, Malvin Jefri, Carl Ernst
Some intellectual disability (ID) syndromes are caused by a mutation in a single gene and have been the focus of therapeutic intervention attempts such as Fragile X and Rett Syndrome, albeit with limited success. The rate at which new drugs are discovered and tested in humans for ID is progressing at a relatively slow pace, and this is particularly true for rare diseases where so few patients make high-quality clinical trials challenging. We discuss how new advances in human stem cell reprogramming and gene editing can facilitate preclinical study design and propose new workflows for how the preclinical to clinical trajectory might proceed given the small number of subjects available in rare monogenic ID syndromes...
October 6, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29040583/taste-receptor-polymorphisms-and-male-infertility
#13
M Gentiluomo, L Crifasi, A Luddi, D Locci, R Barale, P Piomboni, D Campa
STUDY QUESTION: Are polymorphisms of taste receptor genes associated with male infertility? SUMMARY ANSWER: This study has showed the associations between three single nucleotide polymorphisms (SNPs) in taste receptors genes (TASR) and male infertility. WHAT IS KNOWN ALREADY: Recent studies showed the expression of taste receptors in the testis and in spermatozoa, suggesting their possible role in infertility. The vast genetic variability in taste genes results in a large degree of diversity in various human phenotypes...
October 12, 2017: Human Reproduction
https://www.readbyqxmd.com/read/29040558/constitutively-active-fgfr3-disrupts-primary-cilium-length-and-ift20-trafficking-in-various-chondrocyte-models-of-achondroplasia
#14
Ludovic Martin, Nabil Kaci, Valentin Estibals, Nicolas Goudin, Meriem Garfa-Traore, Catherine Benoist-Lasselin, Emilie Dambroise, Laurence Legeai-Mallet
FGFR3 (fibroblast growth factor receptor 3) gain-of-function mutations cause dwarfisms, including achondroplasia (ACH) and thanatophoric dysplasia (TD). The constitutive activation of FGFR3 disrupts the normal process of skeletal growth. Bone-growth anomalies have been identified in skeletal ciliopathies, in which primary cilia (PC) function is disrupted. In human ACH and TD, the impact of FGFR3 mutations on PC in growth plate cartilage remains unknown. Here we showed that in chondrocytes from human (ACH, TD) and mouse Fgfr3Y367C/+ cartilage, the constitutively-active FGFR3 perturbed PC length and the sorting and trafficking of IFT20 to the PC...
October 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29040546/variation-and-functional-impact-of-neanderthal-ancestry-in-western-asia
#15
Recep Ozgur Taskent, Duha Alioglu, Evrim Fer, Handan Melike Donertas, Mehmet Somel, Omer Gokcumen
Neanderthals contributed genetic material to modern humans via multiple admixture events. Initial admixture events presumably occurred in Western Asia shortly after humans migrated out-of-Africa. Despite being a focal point of admixture, earlier studies indicate lower Neanderthal introgression rates in some Western Asian populations as compared to other Eurasian populations. To better understand the genome-wide and phenotypic impact of Neanderthal introgression in the region, we sequenced whole genomes of 10 present-day Europeans, Africans, and the Western Asian Druze at high depth, and analyzed available whole genome data from various other populations, including 16 genomes from present-day Turkey...
October 13, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29040431/prevention-of-breast-cancer-induced-osteolytic-bone-resorption-by-benzyl-isothiocyanate
#16
Subrata K Pore, Eun-Ryeong Hahm, Joseph D Latoche, Carolyn J Anderson, Yongli Shuai, Shivendra V Singh
Osteolytic bone resorption is the primary cause of pain and suffering (e.g., pathological bone fracture) in women with metastatic breast cancer. The current standard of care for patients with bone metastasis for reducing the incidence of skeletal complications includes bisphosphonates and a humanized antibody (denosumab). However, a subset of patients on these therapies still develops new bone metastasis or experience adverse effects. Moreover, some bisphosphonates have poor oral bioavailability. Therefore, orally-bioavailable and non-toxic inhibitors of breast cancer-induced osteolytic bone resorption are still clinically desirable...
October 11, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29040403/age-related-changes-in-temporal-processing-of-rapidly-presented-sound-sequences-in-the-macaque-auditory-cortex
#17
Ng Chi-Wing, Gregg H Recanzone
The mammalian auditory cortex is necessary to resolve temporal features in rapidly-changing sound streams. This capability is crucial for speech comprehension in humans and declines with normal aging. Nonhuman primate studies have revealed detrimental effects of normal aging on the auditory nervous system, and yet the underlying influence on temporal processing remains less well-defined. Therefore, we recorded from the core and lateral belt areas of auditory cortex when awake young and old monkeys listened to tone-pip and noise-burst sound sequences...
October 13, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29040401/a-young-blood-environment-decreases-aging-of-senile-mice-kidneys
#18
Qi Huang, Yichun Ning, Dong Liu, Ying Zhang, Diangeng Li, Yinping Zhang, Zhong Yin, Bo Fu, Guangyan Cai, Xuefeng Sun, Xiangmei Chen
Whether changes in internal body environment affect kidney aging remains unclear. Specifically, it is unknown whether transplanted kidneys from older donors recover from tissue damage after placement in younger recipients. In this study, a parabiosis animal model was established to investigate the effects of a young internal body environment on aged kidneys. The animals were divided into six groups: young (Ycon) and old (Ocon) control groups, isochronic youth-youth group (Y-IP), elderly-elderly group (O-IP) and heterochronic youth (Y-HP) elderly (O-HP) group...
October 13, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29040392/%C3%AE-cypermethrin-and-its-metabolite-3-phenoxybenzoic-acid-exhibit-immunotoxicity-in-murine-macrophages
#19
Xia Wang, Bingnan He, Baida Kong, Lai Wei, Rong Wang, Chenqian Zhou, Yiyan Shao, Jiajia Lin, Yuanxiang Jin, Zhengwei Fu
β-Cypermethrin (β-CYP), one of most important pyrethroids, is widely used to control insects, and has been detected in organisms, including human. Pyrethroids have been shown to pose neurotoxicity, hepatotoxicity, endocrine disruption and reproductive risks in mammals. However, research in immunotoxicity of pyrethroids, especially their metabolites, is limited. A common metabolite of pyrethroids is 3-phenoxybenzoic acid (3-PBA) in mammals. Thus, in this study, we evaluated the immunotoxicity of β-CYP and 3-PBA in mouse macrophages, RAW 264...
October 11, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29040385/a-benchmarking-of-workflows-for-detecting-differential-splicing-and-differential-expression-at-isoform-level-in-human-rna-seq-studies
#20
Gabriela A Merino, Ana Conesa, Elmer A Fernández
Over the last few years, RNA-seq has been used to study alterations in alternative splicing related to several diseases. Bioinformatics workflows used to perform these studies can be divided into two groups, those finding changes in the absolute isoform expression and those studying differential splicing. Many computational methods for transcriptomics analysis have been developed, evaluated and compared; however, there are not enough reports of systematic and objective assessment of processing pipelines as a whole...
October 13, 2017: Briefings in Bioinformatics
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