Chemokines at the Crossroad of Diabetes-Tuberculosis Synergy

The epidemic increase in diabetes mellitus (DM) is taking place in the world were one third of the population is latently infected with tuberculosis (TB). DM, as a chronic metabolic disease, weakens the immune system and increases the risk of Mycobacterium tuberculosis (M.tb) infection. In those who are already latently infected, it increases the risk of reactivation. This is called DM-TB synergy. While the role of immune cells and cytokines has been well studied in DM-TB synergy, the role played by chemokines is largely unrecognized. Chemokines are low molecular weight proteins that are rapidly secreted by both immune and non-immune cells and guide the directorial migration of these cells. Impairment in chemokine secretion or signaling can lead to delayed immune response and can mediate DM-TB synergy. This chapter describes the role played by various chemokines and their receptors in DM-TB synergy

Visual Behavior, Pupil Dilation, and Ability to Identify Emotions From Facial Expressions After Stroke

[EN] Social cognition is the innate human ability to interpret the emotional state of others from contextual verbal and non-verbal information, and to self-regulate accordingly. Facial expressions are one of the most relevant sources of non-verbal communication, and their interpretation has been extensively investigated in the literature, using both behavioral and physiological measures, such as those derived from visual activity and visual responses. The decoding of facial expressions of emotion is performed by conscious and unconscious cognitive processes that involve a complex brain network that can be damaged after cerebrovascular accidents. A diminished ability to identify facial expressions of emotion has been reported after stroke, which has traditionally been attributed to impaired emotional processing. While this can be true, an alteration in visual behavior after brain injury could also negatively contribute to this ability. This study investigated the accuracy, distribution of responses, visual behavior, and pupil dilation of individuals with stroke while identifying emotional facial expressions. Our results corroborated impaired performance after stroke and exhibited decreased attention to the eyes, evidenced by a diminished time and number of fixations made in this area in comparison to healthy subjects and comparable pupil dilation. The differences in visual behavior reached statistical significance in some emotions when comparing individuals with stroke with impaired performance with healthy subjects, but not when individuals post-stroke with comparable performance were considered. The performance dependence of visual behavior, although not determinant, might indicate that altered visual behavior could be a negatively contributing factor for emotion recognition from facial expressions.This study was funded by Conselleria de Educacion, Cultura y Deporte of Generalitat Valenciana of Spain (Project SEJI/2019/017), and Universitat Politecnica de Valencia (Grant PAID-10-18).Maza, A.; Moliner, B.; Ferri, J.; Llorens Rodríguez, R. (2020). Visual Behavior, Pupil Dilation, and Ability to Identify Emotions From Facial Expressions After Stroke. Frontiers in Neurology. 10:1-12. https://doi.org/10.3389/fneur.2019.01415S11210Nijsse, B., Spikman, J. M., Visser-Meily, J. M. A., de Kort, P. L. M., & van Heugten, C. M. (2019). Social cognition impairments are associated with behavioural changes in the long term after stroke. PLOS ONE, 14(3), e0213725. doi:10.1371/journal.pone.0213725Feldman, R. S., White, J. B., & Lobato, D. (1982). Social Skills and Nonverbal Behavior. 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IEEE Transactions on Affective Computing, 12(3), 707-721. doi:10.1109/taffc.2018.2887267Smith, M. L., Grühn, D., Bevitt, A., Ellis, M., Ciripan, O., Scrimgeour, S., … Ewing, L. (2018). Transmitting and decoding facial expressions of emotion during healthy aging: More similarities than differences. Journal of Vision, 18(9), 10. doi:10.1167/18.9.10Thompson, A. E., & Voyer, D. (2014). Sex differences in the ability to recognise non-verbal displays of emotion: A meta-analysis. Cognition and Emotion, 28(7), 1164-1195. doi:10.1080/02699931.2013.875889Doležal, J., & Fabian, V. (2015). 41. Application of eye tracking in neuroscience. Clinical Neurophysiology, 126(3), e44. doi:10.1016/j.clinph.2014.10.200Guo, K. (2012). Holistic Gaze Strategy to Categorize Facial Expression of Varying Intensities. PLoS ONE, 7(8), e42585. doi:10.1371/journal.pone.0042585Guo, K., Soornack, Y., & Settle, R. (2019). 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K., Guerra-Carrillo, B., Miller Singley, A. T., & Bunge, S. A. (2017). Beyond eye gaze: What else can eyetracking reveal about cognition and cognitive development? Developmental Cognitive Neuroscience, 25, 69-91. doi:10.1016/j.dcn.2016.11.001Ariel, R., & Castel, A. D. (2013). Eyes wide open: enhanced pupil dilation when selectively studying important information. Experimental Brain Research, 232(1), 337-344. doi:10.1007/s00221-013-3744-5Zekveld, A. A., & Kramer, S. E. (2014). Cognitive processing load across a wide range of listening conditions: Insights from pupillometry. Psychophysiology, 51(3), 277-284. doi:10.1111/psyp.12151De Gee, J. W., Knapen, T., & Donner, T. H. (2014). Decision-related pupil dilation reflects upcoming choice and individual bias. Proceedings of the National Academy of Sciences, 111(5), E618-E625. doi:10.1073/pnas.1317557111Bradley, M. M., Miccoli, L., Escrig, M. A., & Lang, P. J. (2008). The pupil as a measure of emotional arousal and autonomic activation. Psychophysiology, 45(4), 602-607. doi:10.1111/j.1469-8986.2008.00654.xDuque, A., Sanchez, A., & Vazquez, C. (2014). Gaze-fixation and pupil dilation in the processing of emotional faces: The role of rumination. Cognition and Emotion, 28(8), 1347-1366. doi:10.1080/02699931.2014.881327Lanata, A., Armato, A., Valenza, G., & Scilingo, E. P. (2011). Eye tracking and pupil size variation as response to affective stimuli: a preliminary study. Proceedings of the 5th International ICST Conference on Pervasive Computing Technologies for Healthcare. doi:10.4108/icst.pervasivehealth.2011.246056Peinkhofer, C., Knudsen, G. M., Moretti, R., & Kondziella, D. (2019). Cortical modulation of pupillary function: systematic review. PeerJ, 7, e6882. doi:10.7717/peerj.6882Grill-Spector, K., Knouf, N., & Kanwisher, N. (2004). The fusiform face area subserves face perception, not generic within-category identification. Nature Neuroscience, 7(5), 555-562. doi:10.1038/nn1224Ferretti, V., & Papaleo, F. (2018). Understanding others: emotion recognition abilities in humans and other animals. Genes, Brain and Behavior, e12544. doi:10.1111/gbb.12544Sergerie, K., Chochol, C., & Armony, J. L. (2008). The role of the amygdala in emotional processing: A quantitative meta-analysis of functional neuroimaging studies. Neuroscience & Biobehavioral Reviews, 32(4), 811-830. doi:10.1016/j.neubiorev.2007.12.002Rapcsak, S. Z., Galper, S. R., Comer, J. F., Reminger, S. L., Nielsen, L., Kaszniak, A. W., … Cohen, R. A. (2000). Fear recognition deficits after focal brain damage: A cautionary note. Neurology, 54(3), 575-575. doi:10.1212/wnl.54.3.575Radice-Neumann, D., Zupan, B., Tomita, M., & Willer, B. (2009). Training Emotional Processing in Persons With Brain Injury. Journal of Head Trauma Rehabilitation, 24(5), 313-323. doi:10.1097/htr.0b013e3181b09160Yuvaraj, R., Murugappan, M., Norlinah, M. I., Sundaraj, K., & Khairiyah, M. (2013). Review of Emotion Recognition in Stroke Patients. Dementia and Geriatric Cognitive Disorders, 36(3-4), 179-196. doi:10.1159/000353440Babbage, D. R., Yim, J., Zupan, B., Neumann, D., Tomita, M. R., & Willer, B. (2011). Meta-analysis of facial affect recognition difficulties after traumatic brain injury. Neuropsychology, 25(3), 277-285. doi:10.1037/a0021908Milders, M., Fuchs, S., & Crawford, J. R. (2003). Neuropsychological Impairments and Changes in Emotional and Social Behaviour Following Severe Traumatic Brain Injury. Journal of Clinical and Experimental Neuropsychology, 25(2), 157-172. doi:10.1076/jcen.25.2.157.13642Genova, H. M., Genualdi, A., Goverover, Y., Chiaravalloti, N. D., Marino, C., & Lengenfelder, J. (2016). An investigation of the impact of facial affect recognition impairments in moderate to severe TBI on fatigue, depression, and quality of life. Social Neuroscience, 12(3), 303-307. doi:10.1080/17470919.2016.1173584Rigon, A., Voss, M. W., Turkstra, L. S., Mutlu, B., & Duff, M. C. (2018). 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The perception of positive and negative facial expressions by unilateral stroke patients. Brain and Cognition, 86, 42-54. doi:10.1016/j.bandc.2014.01.017Delazer, M., Sojer, M., Ellmerer, P., Boehme, C., & Benke, T. (2018). Eye-Tracking Provides a Sensitive Measure of Exploration Deficits After Acute Right MCA Stroke. Frontiers in Neurology, 9. doi:10.3389/fneur.2018.00359Lech, M., Kucewicz, M. T., & Czyżewski, A. (2019). Human Computer Interface for Tracking Eye Movements Improves Assessment and Diagnosis of Patients With Acquired Brain Injuries. Frontiers in Neurology, 10. doi:10.3389/fneur.2019.00006Spikman, J. M., Milders, M. V., Visser-Keizer, A. C., Westerhof-Evers, H. J., Herben-Dekker, M., & van der Naalt, J. (2013). Deficits in Facial Emotion Recognition Indicate Behavioral Changes and Impaired Self-Awareness after Moderate to Severe Traumatic Brain Injury. PLoS ONE, 8(6), e65581. doi:10.1371/journal.pone.0065581Knox, L., & Douglas, J. (2009). 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Frontiers in Neural Circuits, 12. doi:10.3389/fncir.2018.0002

8,8-Dimethyl-8,9-dihydro-7H-chromeno[2,3-b]quinoline-10,12-dione

In the title compound, C18H15NO3, the fused benzopyran and pyridine rings are essentially coplanar [r.m.s. deviation = 0.0533 Å with a maximum deviation of 0.080 (1) Å for a benzene C atom]. The cyclohexanone ring adopts an envelope conformation with the dimethyl-substituted C atom 0.660 (2) Å out of the plane formed by the remaining ring atoms (r.m.s. deviation = 0.0305 Å). The dihedral angle between the mean planes of the pyran and cyclohexanone rings is 12.95 (6)°. In the crystal, molecules are linked via C—H...O hydrogen bonds, leading to chains running along [011]

2-Chloro-8,8-dimethyl-8,9-dihydro-7H-chromeno[2,3-b]quinoline-10,12-dione

The asymmetric unit of the title compound, C18H14ClNO3, contains two independent molecules (A and B). In both molecules, the cyclohexanone ring has a chair conformation. The dihedral angles between the pyran ring and the pyridine and chlorophenyl rings are 2.13 (9) and 2.19 (9)°, respectively, in A, and 0.82 (9) and 1.93 (9)°, respectively, in B. The carbonyl O atoms deviate from the pyran and benzene rings to which they are attached by −0.092 (2) and 0.064 (2) Å, respectively, in A, and by −0.080 (2) and −0.063 (2) Å, respectively, in B. In the crystal, the A molecules are linked via C—H...O hydrogen bonds, forming double-stranded chains along [100]. They lie parallel to the double-stranded chains formed by the B molecules, which are also linked via C—H...O hydrogen bonds. The chains stack up the c axis in an –A–A–B–B–A–A– manner, with a number of π–π interactions involving A and B molecules; the centroid–centroid distances vary from 3.4862 (11) to 3.6848 (11) &#197

Measles virus nucleocapsid protein modulates the Signal Regulatory Protein-β1 (SIRPβ1) to enhance osteoclast differentiation in Paget's disease of bone

Paget's disease of bone (PDB) is a chronic localized bone disorder in an elderly population. Environmental factors such as paramyxovirus are implicated in PDB and measles virus nucleocapsid protein (MVNP) has been shown to induce pagetic osteoclasts (OCLs). However, the molecular mechanisms underlying MVNP stimulation of OCL differentiation in the PDB are unclear. We therefore determined the MVNP regulated gene expression profiling during OCL differentiation. Agilent microarray analysis of gene expression identified high levels of SIRPβ1 (353-fold) expression in MVNP transduced human bone marrow mononuclear cells stimulated with RANKL. Real-time PCR analysis further confirmed that MVNP alone upregulates SIRPβ1 mRNA expression in these cells. Also, bone marrow mononuclear cells derived from patients with PDB showed high levels of SIRPβ1 mRNA expression compared to normal subjects. We further show that MVNP increases SIRPβ1 interaction with DAP12 adaptor protein in the presence and absence of RANKL stimulation. shRNA knockdown of SIRPβ1 expression in normal human bone marrow monocytes decreased the levels of MVNP enhanced p-Syk and c-Fos expression. In addition, SIRPβ1 knockdown significantly decreased MVNP stimulated dendritic cell–specific transmembrane protein (DC-STAMP) and connective tissue growth factor (CTGF) mRNA expression during OCL differentiation. Furthermore, we demonstrated the contribution of SIRPβ1 in MVNP induced OCL formation and bone resorption. Thus, our results suggest that MVNP modulation of SIRPβ1 provides new insights into the molecular mechanisms which control high bone turnover in PDB

Measles virus nucleocapsid protein modulates the Signal Regulatory Protein-β1 (SIRPβ1) to enhance osteoclast differentiation in Paget\u27s disease of bone

Paget\u27s disease of bone (PDB) is a chronic localized bone disorder in an elderly population. Environmental factors such as paramyxovirus are implicated in PDB and measles virus nucleocapsid protein (MVNP) has been shown to induce pagetic osteoclasts (OCLs). However, the molecular mechanisms underlying MVNP stimulation of OCL differentiation in the PDB are unclear. We therefore determined the MVNP regulated gene expression profiling during OCL differentiation. Agilent microarray analysis of gene expression identified high levels of SIRPβ1 (353-fold) expression in MVNP transduced human bone marrow mononuclear cells stimulated with RANKL. Real-time PCR analysis further confirmed that MVNP alone upregulates SIRPβ1 mRNA expression in these cells. Also, bone marrow mononuclear cells derived from patients with PDB showed high levels of SIRPβ1 mRNA expression compared to normal subjects. We further show that MVNP increases SIRPβ1 interaction with DAP12 adaptor protein in the presence and absence of RANKL stimulation. shRNA knockdown of SIRPβ1 expression in normal human bone marrow monocytes decreased the levels of MVNP enhanced p-Syk and c-Fos expression. In addition, SIRPβ1 knockdown significantly decreased MVNP stimulated dendritic cell-specific transmembrane protein (DC-STAMP) and connective tissue growth factor (CTGF) mRNA expression during OCL differentiation. Furthermore, we demonstrated the contribution of SIRPβ1 in MVNP induced OCL formation and bone resorption. Thus, our results suggest that MVNP modulation of SIRPβ1 provides new insights into the molecular mechanisms which control high bone turnover in PDB