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R PranavKumar Shadamarshan, Harini Balaji, Harsha Shrihari Rao, K Balagangadharan, S Viji Chandran, N Selvamurugan
Trans-anethole (TA) is a phenolic phytocompound widely used in the food and health sector because of its diverse biological properties. However, its role in the promotion of bone formation is not known. With the enhanced bioavailability of TA, we aimed to determine its effect on osteogenesis; TA at different concentrations (5, 10, and 20 μM) was loaded onto polycaprolactone (PCL)/polyvinylpyrrolidone (PVP) fibers by the electrospinning technique. The synthesized PCL/PVP + TA fibers were subjected to physiochemical and material characterization...
August 8, 2018: Colloids and Surfaces. B, Biointerfaces
Jennifer M Caron, XiangHua Han, Liangru Contois, Calvin P H Vary, Peter C Brooks
Stromal components not only help form the structure of neoplasms such as melanomas, but they functionally contribute to their malignant phenotype. Thus, uncovering signaling pathways that integrate the behavior of both tumor and stromal cells may provide unique opportunities for the development of more effective strategies to control tumor progression. In this regard, extracellular matrix-mediated signaling plays a role in coordinating the behavior of both tumor and stromal cells. Here we provide evidence that targeting a cryptic region of the extracellular matrix protein collagen (HU177 epitope) inhibits melanoma tumor growth and metastasis and reduces angiogenesis and the accumulation of αSMA-expressing stromal cell in these tumors...
August 14, 2018: American Journal of Pathology
Olga Pereira, Alexandra Teixeira, Belém Sampaio-Marques, Isabel Castro, Henrique Girão, Paula Ludovico
Acute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient-sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial...
August 17, 2018: Journal of Cellular and Molecular Medicine
Armando Angulo-Chavira, Natalia Arias-Trejo
A mediated priming effect refers to the activation of a target via a mediator previously activated by a prime. This effect has been found at 24 months of age for phono-semantic links: a prime ( cup) activates a target ( dog) via a mediator ( cat), providing evidence of activation in a forward direction (phonological to semantic). Interactive models, however, propose that activation propagates in both forward and backward directions between processing levels. This study investigated the development of bidirectional co-activation of phonological and semantic levels of processing in Spanish-speaking toddlers...
September 2018: Quarterly Journal of Experimental Psychology: QJEP
Samantha E Yohn, Daniel J Foster, Dan P Covey, Mark S Moehle, Jordan Galbraith, Pedro M Garcia-Barrantes, Hyekyung P Cho, Michael Bubser, Anna L Blobaum, Max E Joffe, Joseph F Cheer, Carrie K Jones, Craig W Lindsley, P Jeffrey Conn
Recent clinical and preclinical studies suggest that selective activators of the M4 muscarinic acetylcholine receptor have potential as a novel treatment for schizophrenia. M4 activation inhibits striatal dopamine release by mobilizing endocannabinoids, providing a mechanism for local effects on dopamine signaling in the striatum but not in extrastriatal areas. G protein-coupled receptors (GPCRs) typically induce endocannabinoid release through activation of Gαq/11 -type G proteins whereas M4 transduction occurs through Gαi/o -type G proteins...
August 16, 2018: Molecular Psychiatry
Robert Ryley Parrish, Neela J Codadu, Claudia Racca, Andrew J Trevelyan
Changes in gene expression are an important mechanism by which activity levels are regulated in the nervous system. It is not known, however, how network activity influences gene expression in interneurons: since they themselves provide negative feedback in the form of synaptic inhibition, there exists a potential conflict between their cellular homeostatic tendencies, and those of the network. We present a means of examining this issue, utilising simple in vitro models showing different patterns of intense network activity...
August 15, 2018: Journal of Neurophysiology
Wulfram Gerstner, Marco Lehmann, Vasiliki Liakoni, Dane Corneil, Johanni Brea
Most elementary behaviors such as moving the arm to grasp an object or walking into the next room to explore a museum evolve on the time scale of seconds; in contrast, neuronal action potentials occur on the time scale of a few milliseconds. Learning rules of the brain must therefore bridge the gap between these two different time scales. Modern theories of synaptic plasticity have postulated that the co-activation of pre- and postsynaptic neurons sets a flag at the synapse, called an eligibility trace, that leads to a weight change only if an additional factor is present while the flag is set...
2018: Frontiers in Neural Circuits
Mallory C Campbell, Laura Pontiggia, Ashley Y Russell, Roland Schwarting, Jeanette Camacho, Jean-Francois Jasmin, Isabelle Mercier
Breast cancers (BCas) that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are referred to as triple negative breast cancers (TNBCs) and have the poorest clinical outcome. Once these aggressive tumors progress to distant organs, the median survival decreases to 12 months. With endocrine therapies being ineffective in this BCa subtype, highly toxic chemo- and radiation therapies are the only options. A better understanding of the functional role(s) of molecular targets contributing to TNBC progression could help in the design and development of new treatments that are more targeted with less toxicity...
July 13, 2018: Oncotarget
Aglieri Virginia, Chaminade Thierry, Takerkart Sylvain, Belin Pascal
Recognizing who is speaking is a cognitive ability characterized by considerable individual differences, which could relate to the inter-individual variability observed in voice-elicited BOLD activity. Since voice perception is sustained by a complex brain network involving temporal voice areas (TVAs) and, even if less consistently, extra-temporal regions such as frontal cortices, functional connectivity (FC) during an fMRI voice localizer (passive listening of voices vs non-voices) has been computed within twelve temporal and frontal voice-sensitive regions ("voice patches") individually defined for each subject (N = 90) to account for inter-individual variability...
August 9, 2018: NeuroImage
Haibin Tian, Jing-Ying Xu, Yu Tian, Yaqi Cao, Chunpin Lian, Qingjian Ou, Binxin Wu, Caixia Jin, Furong Gao, Juan Wang, Jieping Zhang, Jingfa Zhang, Weiye Li, Lixia Lu, Guo-Tong Xu
The pathological change of retinal pigment epithelial (RPE) cells is one of the main reasons for the development of age-related macular degeneration (AMD). Thus, cultured RPE cells are a proper cell model for studying the etiology of AMD in vitro. However, such cultured RPE cells easily undergo epithelial-mesenchymal transition (EMT) that results in changes of cellular morphology and functions of the cells. To restore and maintain the mesenchymal-epithelial transition (MET) of the cultured RPE cells, we cultivated dedifferentiated porcine RPE (pRPE) cells and compared their behaviors in four conditions: 1) in cell culture dishes with DMEM/F12 containing FBS (CC dish-FBS), 2) in petri dishes with DMEM/F12 containing FBS (Petri dish-FBS), 3) in cell culture dishes with DMEM/F12 containing N2 and B27 supplements (CC dish-N2B27), and 4) in petri dishes with DMEM/F12 containing N2 and B27 (Petri dish-N2B27)...
August 7, 2018: Experimental Eye Research
Carole Le Coz, Brian E Nolan, Melissa Trofa, Alicia M Kamsheh, Mustafa K Khokha, Saquib A Lakhani, Antonio Novelli, Elaine H Zackai, Kathleen E Sullivan, Silvana Briuglia, Tricia R Bhatti, Neil Romberg
Located contiguously on the long arm of the second chromosome are gene paralogs encoding the immunoglobulin-family co-activation receptors CD28 and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). CD28 and CTLA4 share the same B7 ligands yet each provides opposing proliferative signals to T cells. Herein, we describe for the first time two unrelated subjects with coexisting CD28 and CTLA4 haploinsufficiency due to heterozygous microdeletions of chromosome 2q. Although their clinical phenotype, multi-organ inflammatory disease, is superficially similar to that of CTLA4 haploinsufficient autoimmune lymphoproliferative syndrome type V (ALPS5) patients, we demonstrate our subjects' underlying immunopathology to be distinct...
2018: Frontiers in Immunology
Patrick Nyman, Darya Buehler, Paul F Lambert
PURPOSE: Head and neck squamous cell carcinoma (HNSCC), a common cancer worldwide, is etiologically associated with tobacco use, high alcohol consumption and high risk human papillomaviruses (HPV). The Notch signaling pathway, which is involved in cell differentiation decisions with differential downstream targets and effects depending on tissue type and developmental stage, has been implicated in human HNSCC. Notch1 is among the most frequently mutated genes in both HPV-positive and HPV-negative HNSCC...
August 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Didel M Mahounga, Hui Sun, Yong Liang Jiang
The CO2 -concentrating mechanism (CCM) has evolved to improve the efficiency of photosynthesis in autotrophic cyanobacteria. CmpR, a LysR-type transcriptional regulator (LTTR) from Synechococcus elongatus PCC 7942, was found to regulate CCM-related genes under low-CO2 conditions. Here, the dimeric structure of the effector-binding domain of CmpR (CmpR-EBD) in complex with the co-activator ribulose 1,5-bisphosphate (RuBP) is reported at 2.15 Å resolution. One RuBP molecule binds to the inter-domain cleft between the two subunits of the CmpR-EBD dimer...
August 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
Andrei V Chernov, Albert G Remacle, Swathi K Hullugundi, Piotr Cieplak, Mila Angert, Jennifer Dolkas, Veronica I Shubayev, Alex Y Strongin
Neurotrauma frequently results in neuropathic pain. Our earlier studies revealed that peripheral neurotrauma-induced fragmentation of the myelin basic protein (MBP), a major component of the myelin sheath formed by Schwann cells, initiates a pain response from light touch stimuli (mechanical allodynia) in rodents. Here, we identified the cyclin-dependent kinase 5 (CDK5), as an intracellular interactor of MBP in Schwann cells. The algesic peptide fragment of MBP directly associated with CDK5. When complexed with its p25 co-activator, CDK5 phosphorylated the conserved MBP sequence...
August 6, 2018: FEBS Journal
Nam Hee Kim, Yoonmi Lee, Jong In Yook
As highly conserved signaling cascades of multicellular organisms, Wnt and Hippo pathways control a wide range of cellular activities, including cell adhesion, fate determination, cell cycle, motility, polarity, and metabolism. Dysregulation of those pathways are implicated in many human diseases, including cancer. Similarly to β-catenin in the Wnt pathway, the YAP transcription co-activator is a major player in Hippo. Although the intracellular dynamics of YAP are well-known to largely depend on phosphorylation by LATS and AMPK kinases, the molecular effector of YAP cytosolic translocation remains unidentified...
August 6, 2018: BMB Reports
Mindy F Levin, John M Solomon, Akash Shah, Andréanne K Blanchette, Anatol G Feldman
OBJECTIVES: Deficits in regulation of tonic stretch reflex thresholds (TSRTs) after stroke occur in elbow flexors and extensors leading to spasticity in specific joint ranges. Threshold deregulation may also be responsible for other deficits such as abnormal activation of passively shortening muscles. Goals were to characterize activation of shortening elbow extensors during passive elbow flexor stretch in individuals with stroke, and identify its relationship to upper-limb motor impairment...
July 24, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Mark C Horowitz, Steven M Tommasini
PGC-1α is a transcriptional co-activator associated with PPARγ that regulates thermogenic gene expression in brown fat. In this issue, Yu et al. (2018) show that PGC-1α regulates marrow mesenchymal stromal cell lineage allocation in vivo, inhibiting marrow adipogenesis and associated bone loss in the aging skeleton and following ovariectomy-induced osteoporosis.
August 2, 2018: Cell Stem Cell
Thomas E Kraynak, Anna L Marsland, Tor D Wager, Peter J Gianaros
Communication between the brain and peripheral mediators of systemic inflammation is implicated in numerous psychological, behavioral, and physiological processes. Functional neuroimaging studies have identified brain regions that associate with peripheral inflammation in humans, yet there are open questions about the consistency, specificity, and network characteristics of these findings. The present systematic review provides a meta-analysis to address these questions. Multilevel kernel density analysis of 24 studies (37 statistical maps; 264 coordinates; 457 participants) revealed consistent effects in the amygdala, hippocampus, hypothalamus, striatum, insula, midbrain, and brainstem, as well as prefrontal and temporal cortices...
July 29, 2018: Neuroscience and Biobehavioral Reviews
Nicolas Fougeront, Bernard Fleiter
According to the "pain adaptation model", temporomandibular disorder (TMD)-related pain induces a paradoxical activity of masticatory muscles: an agonistic hypoactivity during jaw closing and an antagonistic activity during jaw opening (agonist/antagonist co-activation). However, this model suffers several weaknesses, notably it does not explain all types of neck muscle activities in neck pain (NP) which is a very prevalent TMD co-morbid condition. In NP, neck muscle antagonistic activity is increased, and agonistic activity is decreased as postulated by the pain adaptation model...
August 1, 2018: Canadian Journal of Physiology and Pharmacology
Esther M J Bekkers, Sam Van Rossom, Elke Heremans, Kim Dockx, Surendar Devan, Sabine M P Verschueren, Alice Nieuwboer
Introduction: Freezing of gait (FOG) is a powerful determinant of falls in Parkinson's disease (PD). Automatic postural reactions serve as a protective strategy to prevent falling after perturbations. However, differences in automatic postural reactions between patients with and without FOG in response to perturbation are at present unclear. Therefore, the present study aimed to compare the response patterns and neuromuscular control between PD patients with and without FOG and healthy controls (HCs) after postural perturbations...
2018: Frontiers in Neurology
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