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Max D Wellenstein, Karin E de Visser
Owing to their tremendous diversity and plasticity, immune cells exert multifaceted functions in tumor-bearing hosts, ranging from anti-tumor to pro-tumor activities. Tumor immune landscapes differ greatly between and within cancer types. Emerging evidence suggests that genetic aberrations in cancer cells dictate the immune contexture of tumors. Here, we review the current understanding of the mechanisms whereby common drivers of tumorigenesis modulate the tumor immune milieu. We discuss these findings in the context of clinical observations and examine how cancer-cell-intrinsic properties can be exploited to maximize the benefit of immunomodulatory therapies...
March 20, 2018: Immunity
Tadashi Nomura, Wataru Yamashita, Hitoshi Gotoh, Katsuhiko Ono
Highly ordered brain architectures in vertebrates consist of multiple neuron subtypes with specific neuronal connections. However, the origin of and evolutionary changes in neuron specification mechanisms remain unclear. Here, we report that regulatory mechanisms of neuron subtype specification are divergent in developing amniote brains. In the mammalian neocortex, the transcription factors (TFs) Ctip2 and Satb2 are differentially expressed in layer-specific neurons. In contrast, these TFs are co-localized in reptilian and avian dorsal pallial neurons...
March 20, 2018: Cell Reports
Manami Yamashita, Shin-Ya Kawaguchi, Tetsuya Hori, Tomoyuki Takahashi
Synaptic efficacy plays crucial roles in neuronal circuit operation and synaptic plasticity. Presynaptic determinants of synaptic efficacy are neurotransmitter content in synaptic vesicles and the number of vesicles undergoing exocytosis at a time. Bursts of presynaptic firings depress synaptic efficacy, mainly due to depletion of releasable vesicles, whereas recovery from strong depression is initiated by endocytic vesicle retrieval followed by refilling of vesicles with neurotransmitter. We washed out presynaptic cytosolic GABA to induce a rundown of IPSCs at cerebellar inhibitory cell pairs in slices from rats and then allowed fast recovery by elevating GABA concentration using photo-uncaging...
March 20, 2018: Cell Reports
Xu Zheng, Ali Beyzavi, Joanna Krakowiak, Nikit Patel, Ahmad S Khalil, David Pincus
Clonal populations of cells exhibit cell-to-cell variation in the transcription of individual genes. In addition to this noise in gene expression, heterogeneity in the proteome and the proteostasis network expands the phenotypic diversity of a population. Heat shock factor 1 (Hsf1) regulates chaperone gene expression, thereby coupling transcriptional noise to proteostasis. Here we show that cell-to-cell variation in Hsf1 activity is an important determinant of phenotypic plasticity. Budding yeast cells with high Hsf1 activity were enriched for the ability to acquire resistance to an antifungal drug, and this enrichment depended on Hsp90, a known phenotypic capacitor and canonical Hsf1 target...
March 20, 2018: Cell Reports
Adina S Fischer, M Catalina Camacho, Tiffany C Ho, Susan Whitfield-Gabrieli, Ian H Gotlib
Importance: Adolescence is a neurodevelopmental period during which experience-dependent plasticity in brain circuitry may confer vulnerability to depression as well as resilience to disorder. Little is known, however, about the neural mechanisms that underlie resilience during this critical period of brain development. Objective: To examine neural functional connectivity correlates of resilience in adolescent females at high and low familial risk for depression who did and did not develop the disorder...
March 21, 2018: JAMA Psychiatry
Qi Wu, Tomotaka Ogasawara, Nobuhiro Yoshikawa, Hongzhou Zhai
Amorphous thermoplastics, as a type of engineering plastic material, are used in various industrial sectors. In order to manufacture high-performance products, it is important to optimize their forming process to mitigate residual stresses. However, stress in a plate is difficult to measure, therefore, modeling provides a powerful way to investigate and understand the evolution of stress. In this study, the forming process of a polyetherimide (PEI) plate was modelled using finite element analysis, and then validated through a comparison with a warpage experiment...
March 21, 2018: Materials
Katharina Dietrich, Yvonne Bouter, Michael Müller, Thomas A Bayer
This commentary reviews the role of the Alzheimer amyloid peptide Aβ on basal synaptic transmission, synaptic short-term plasticity, as well as short- and long-term potentiation in transgenic mice, with a special focus on N-terminal truncated Aβ4-42 . Aβ4-42 is highly abundant in the brain of Alzheimer's disease (AD) patients. It demonstrates increased neurotoxicity compared to full length Aβ, suggesting an important role in the pathogenesis of AD. Transgenic Tg4-42 mice, a model for sporadic AD, express human Aβ4-42 in Cornu Ammonis (CA1) neurons, and develop age-dependent hippocampal neuron loss and neurological deficits...
March 21, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Luna Jammal, Ben Whalley, Edi Barkai
Training rats in a complex olfactory discrimination task results in acquisition of 'rule learning' (learning how to learn), a term describing the capability to perform the task superbly. Such rule learning results in strengthening of both excitatory and inhibitory synaptic connections between neurons in the piriform cortex. Moreover, intrinsic excitability is also enhanced throughout the pyramidal neuron population. Surprisingly, the cortical network retains its stability under these long-term modifications...
March 21, 2018: Journal of Neurophysiology
KyuHan Kim, Siyoung Q Choi, Joseph A Zasadzinski, Todd M Squires
Microbutton rheometry reveals that the chiral morphology of dipalmitoylphosphatidylcholine (DPPC) monolayers imparts a chiral nonlinear rheological response. The nonlinear elastic modulus and yield stress of DPPC monolayers are greater when sheared clockwise (C), against the natural winding direction of DPPC domains, than counter-clockwise (CC). Under strong CC shear strains, domains deform plastically; by contrast, domains appear to fracture under strong C shearing. After CC shearing, extended LC domains develop regular patterns of new invaginations as they recoil, which we hypothesize reflect the nucleation and growth of new defect lines across which the tilt direction undergoes a step change in orientation...
March 21, 2018: Soft Matter
Saori Furuta, Gang Ren, Jian-Hua Mao, Mina J Bissell
How mammalian tissues maintain their architecture and tissue-specificity is poorly understood. Previously, we documented both the indispensable role of the extracellular matrix (ECM) protein, laminin-111 (LN1), in the formation of normal breast acini, and the phenotypic reversion of cancer cells to acini-like structures in 3-dimensional (3D) gels with inhibitors of oncogenic pathways. Here, we asked how laminin (LN) proteins integrate the signaling pathways necessary for morphogenesis. We report a surprising reciprocal circuitry comprising positive players: laminin-5 (LN5), nitric oxide (NO), p53, HOXD10 and three microRNAs (miRNAs) - that are involved in the formation of mammary acini in 3D...
March 21, 2018: ELife
I Shanmugarajah, M Solhaug, O Aslam, O Reiertsen
BACKGROUND: To assess the efficacy and safety of Endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO). MATERIAL AND METHODS: A review of all ERCP-procedures performed at Akershus University Hospital during the six year period between 2009-2014 was analysed. Data for the period 2009- 2013 were obtained retrospectively and prospectively for 2014. Patients with jaundice due to MBO were selected for the present study. RESULTS: A total of 210 patients (51% females), median age of 70 years (range 33-96) were included...
October 2017: Acta Gastro-enterologica Belgica
Zhao-Xia Cao, An-Guo Liu, Tian-Tian Zhu, Xiao-Juan Li, Yu-Ting Wei, Xing-Ke Yan
Acupuncture has been found effective for the treatment of amblyopia, and its mechanism has been investigated. A review of recently published research results indicated that when used to treat amblyopia, acupuncture induced changes in the action of neurotransmitters in the visual system, promoted the secretion and synthesis of brain-derived neurotrophic factor, and stimulated the expression of genes related to visual plasticity.
March 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Irina Turku, Timo Kärki, Ari Puurtinen
The influence of accelerated weathering, xenon-arc light and freeze-thaw cycling on wood plastic composites extruded from a recycled plastic was studied. The results showed that, in general, weathering had a stronger impact on samples made from plastic waste compared to a sample made from virgin material. After weathering, the mechanical properties, tensile and flexural, were reduced by 2-30%, depending on the plastic source. Wettability of the samples was shown to play a significant role in their stability...
March 2018: Heliyon
Ryosuke Matsuzaki, Takeshi Tachikawa, Junya Ishizuka
Accurate simulations of carbon fiber-reinforced plastic (CFRP) molding are vital for the development of high-quality products. However, such simulations are challenging and previous attempts to improve the accuracy of simulations by incorporating the data acquired from mold monitoring have not been completely successful. Therefore, in the present study, we developed a method to accurately predict various CFRP thermoset molding characteristics based on data assimilation, a process that combines theoretical and experimental values...
March 2018: Heliyon
Ma Cristina Acosta-García, Israel Morales-Reyes, Anabel Jiménez-Anguiano, Nikola Batina, N P Castellanos, R Godínez-Fernández
This paper shows the simultaneous recording of electrical activity and the underlying ionic currents by using a gold substrate to culture NG108-15 cells. Cells grown on two different substrates (plastic Petri dishes and gold substrates) were characterized quantitatively through scanning electron microscopy (SEM) as well as qualitatively by optical and atomic force microscopy (AFM). No significant differences were observed between the surface area of cells cultured on gold substrates and Petri dishes, as indicated by measurements performed on SEM images...
February 2018: Heliyon
Kathleen Griffioen, Mark P Mattson, Eitan Okun
Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by progressive striatal and cortical atrophy, has been strongly linked with neuroinflammation. Toll-like receptors, a family of innate immune receptors, are a major pathway for neuroinflammation with pleiotropic effects on neuronal plasticity and neurodevelopment. We assessed whether deficiency for TLRs 2, 3 or 4 affects life expectancy in the N171-82Q mouse model of HD. Our data indicate that homozygous TLRs 2 and 3 as well as heterozygous TLR4 deficiency significantly extends the life expectancy of HD mice...
January 2018: Heliyon
Tenpei Akita, Kazushi Aoto, Mitsuhiro Kato, Masaaki Shiina, Hiroki Mutoh, Mitsuko Nakashima, Ichiro Kuki, Shin Okazaki, Shinichi Magara, Takashi Shiihara, Kenji Yokochi, Kaori Aiba, Jun Tohyama, Chihiro Ohba, Satoko Miyatake, Noriko Miyake, Kazuhiro Ogata, Atsuo Fukuda, Naomichi Matsumoto, Hirotomo Saitsu
Objective: α ( CAMK2A ) and β ( CAMK2B ) isoforms of Calcium/calmodulin-dependent protein kinase II (CaMKII) play a pivotal role in neuronal plasticity and in learning and memory processes in the brain. Here, we explore the possible involvement of α - and β -CaMKII variants in neurodevelopmental disorders. Methods: Whole-exome sequencing was performed for 976 individuals with intellectual disability, developmental delay, and epilepsy. The effect of CAMK2A and CAMK2B variants on CaMKII structure and firing of neurons was evaluated by computational structural analysis, immunoblotting, and electrophysiological analysis...
March 2018: Annals of Clinical and Translational Neurology
Mohit Kumar Jolly, Prakash Kulkarni, Keith Weninger, John Orban, Herbert Levine
It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms-those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa), the primary standard care for metastatic disease...
2018: Frontiers in Oncology
Laura Hidalgo-Garcia, Julio Galvez, M Elena Rodriguez-Cabezas, Per O Anderson
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract characterized by an exacerbated mucosal immune response. Macrophages play pivotal roles in the maintenance of gut homeostasis but they are also implicated in the pathogenesis of IBD. They are highly plastic cells and their activation state depends on the local environment. In the healthy intestine, resident macrophages display an M2 phenotype characterized by inflammatory energy, while inflammatory M1 macrophages dominate in the inflamed intestinal mucosa...
2018: Frontiers in Pharmacology
Victoria Shabardina, Tabea Kischka, Hanna Kmita, Yutaka Suzuki, Wojciech Makałowski
Amoebozoans are in many aspects interesting research objects, as they combine features of single-cell organisms with complex signaling and defense systems, comparable to multicellular organisms. Acanthamoeba castellanii is a cosmopolitan species and developed diverged feeding abilities and strong anti-bacterial resistance; Entamoeba histolytica is a parasitic amoeba, who underwent massive gene loss and its genome is almost twice smaller than that of A. castellanii . Nevertheless, both species prosper, demonstrating fitness to their specific environments...
2018: International Journal of Biological Sciences
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