IgM-producing tumors in the BALB/c mouse: a model for B-cell maturation

Five adjuvant induced BALB/c tumors producing IgM—McPc 1748, W 3469, TEPC 183, McPc 774, and Y 5781—were characterized morphologically by electron microscopy, analysis of the distribution of surface-bound and intracytoplasmic IgM using immunofluorescence, and by biochemical study of IgM synthesis, turnover, and secretion. The cells of different tumors appear to represent different stages in B-cell maturation when compared to normal, lipopolysaccharide-stimulated B cells. Thus, McPc 1748 tumor cells resemble 10–25-h stimulated normal B cells, 3469 cells resemble 20–35-h stimulated B cells, TEPC 183 cells resemble 45–65-h stimulated B cells, Y 5781 cells resemble 80–110-h stimulated B cells, and McPc 774 cells resemble 100–130-h stimulated B cells

A continuous isotropic-nematic liquid crystalline transition of F-actin solutions

The phase transition from the isotropic (I) to nematic (N) liquid crystalline suspension of F-actin of average length $3~\mu$m or above was studied by local measurements of optical birefringence and protein concentration. Both parameters were detected to be continuous in the transition region, suggesting that the I-N transition is higher than 1st order. This finding is consistent with a recent theory by Lammert, Rokhsar & Toner (PRL, 1993, 70:1650), predicting that the I-N transition may become continuous due to suppression of disclinations. Indeed, few line defects occur in the aligned phase of F-actin. Individual filaments in solutions of a few mg/ml F-actin undergo fast translational diffusion along the filament axis, whereas both lateral and rotational diffusions are suppressed.Comment: 4 pages with 4 figures. Submitted to Physical Review Letter

What Do You Meme? Meme Humor Comprehension in Adolescents with Language Disorder or Hearing Loss

Easy access to the internet allows adolescents to share humor, such as memes, via social media. This quasi-experimental study investigated whether there was a difference in the number of memes comprehended on an assessment test among adolescents who were typically developing, adolescents who were deaf or hard of hearing, and adolescents with language disorders. It also sought to determine if the meme’s picture, whether related to the text or unrelated, contributed to adolescents’ comprehension. Participants were given a short reading screening and a multiple-choice test of meme comprehension. Adolescents who were typically developing out-performed adolescents who were deaf or hard of hearing or who had language disorders. Supporting pictures did not appear to aid in meme comprehension. Findings from this study suggest the need for professionals to include direct instruction of humor when working with adolescents who are deaf or hard of hearing or who have language disorders

A kinematic examination of dual-route processing for action imitation

The dual-route model of imitation suggests that meaningful and meaningless actions are processed through either an indirect or direct route, respectively. Evidence indicates that the direct route is more cognitively demanding, since it relies on mapping visuospatial properties of the observed action on to a performed one. These cognitive demands might negatively influence reaction time and accuracy for actions performed following a meaningless action under time constraints. However, how meaningful and meaningless action imitation processing is reflected in movement kinematics is not yet clear. We wanted to confirm whether meaningless action performance incurs a reaction time cost, whether the cost is reflected in kinematics, and, more generally, to examine kinematic markers of emblematic meaningful and meaningless action imitation. We examined participants’ reaction time and wrist movements when they imitated emblematic meaningful or matched meaningless gestures in either blocks of the same action type, or mixed blocks. Meaningless actions were associated with a greater correction period at the end of the movement, possibly reflecting a strategy designed to ensure accurate completion for less familiar actions under time constraints. Furthermore, in mixed blocks, trials following meaningless actions had a significantly increased reaction time, supporting previous claims that route selection for action imitation may be stimulus-driven. However, there was only convincing evidence for this effect with an interval of ~2948ms, but not ~3573ms or ~2553ms, between movements. Future work motion-tracking the entire hand to assess imitation accuracy, and more closely examining the influence of duration between movements, may help to explain these effects

Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding

<p>Abstract</p> <p>Background</p> <p>Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the <it>trans</it>-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as α-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging. Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1.</p> <p>Results</p> <p>Overexpression of either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K resulted in increased basal APP ectodomain shedding. However, in contrast to the report of Roßner <it>et al </it>(2004), phorbol ester-dependent APP ectodomain shedding from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from that observed following application of phorbol to cells overexpressing APP and Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein reported to be essential for PKC-regulated shedding of pro-EGF, was found to play no obvious role in regulated shedding of sAPPα.</p> <p>Conclusion</p> <p>Our results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP.</p

Validation of a low-cost virtual reality system for training street-crossing. A comparative study in healthy, neglected and non-neglected stroke individuals

Unilateral spatial neglect is a common consequence of stroke that directly affects the performance of activities of daily living. This impairment is traditionally assessed with paper-and-pencil tests that can lack correspondence to real life and are easily compensated. Virtual reality can immerse patients in more ecological scenarios, thus providing therapists with new tools to assess and train the effects of this impairment in simulated real tasks. This paper presents the clinical validation and convergent validity of a low-cost virtual reality system for training street-crossing in stroke patients with and without neglect. The performance of neglect patients was significantly worse than the performance of non-neglect and healthy participants. In addition, several correlations between the scores in the system and in the traditional scales were detected.This study was funded in part by Ministerio de Educacion y Ciencia Spain, Projects Consolider-C (SEJ2006-14301/PSIC), "CIBER of Physiopathology of Obesity and Nutrition, an initiative of ISCIII" and the Excellence Research Program PROMETEO (Generalitat Valenciana. Conselleria de Educacion, 2008-157).Navarro, MD.; Llorens Rodríguez, R.; Noé, E.; Ferri, J.; Alcañiz Raya, ML. (2013). Validation of a low-cost virtual reality system for training street-crossing. A comparative study in healthy, neglected and non-neglected stroke individuals. Neuropsychological Rehabilitation. 23(4):597-618. https://doi.org/10.1080/09602011.2013.806269S597618234Allegri, R. F. (2000). Atención y negligencia: bases neurológicas, evaluación y trastornos. Revista de Neurología, 30(05), 491. doi:10.33588/rn.3005.99645Appelros, P., Karlsson, G. M., Seiger, &#x000C5;ke, & Nydevik, I. (2002). Neglect and Anosognosia After First-Ever Stroke: Incidence and Relationship to Disability. Journal of Rehabilitation Medicine, 34(5), 215-220. doi:10.1080/165019702760279206Baheux, K., Yoshizawa, M., & Yoshida, Y. (2007). Simulating hemispatial neglect with virtual reality. Journal of NeuroEngineering and Rehabilitation, 4(1). doi:10.1186/1743-0003-4-27Boian, R. F., Burdea, G. C., Deutsch, J. E. and Winter, S. H. Street crossing using a virtual environment mobility simulator.Paper presented at 3rd Annual International Workshop on Virtual Reality. Lausanne, Switzerland.Broeren, J., Samuelsson, H., Stibrant-Sunnerhagen, K., Blomstrand, C., & Rydmark, M. (2007). Neglect assessment as an application of virtual reality. Acta Neurologica Scandinavica, 116(3), 157-163. doi:10.1111/j.1600-0404.2007.00821.xBuxbaum, L. J., Ferraro, M. K., Veramonti, T., Farne, A., Whyte, J., Ladavas, E., … Coslett, H. B. (2004). Hemispatial neglect: Subtypes, neuroanatomy, and disability. Neurology, 62(5), 749-756. doi:10.1212/01.wnl.0000113730.73031.f4Buxbaum, L. J., Palermo, M. A., Mastrogiovanni, D., Read, M. S., Rosenberg-Pitonyak, E., Rizzo, A. A., & Coslett, H. B. (2008). Assessment of spatial attention and neglect with a virtual wheelchair navigation task. Journal of Clinical and Experimental Neuropsychology, 30(6), 650-660. doi:10.1080/13803390701625821Castiello, U., Lusher, D., Burton, C., Glover, S., & Disler, P. (2004). Improving left hemispatial neglect using virtual reality. Neurology, 62(11), 1958-1962. doi:10.1212/01.wnl.0000128183.63917.02Conners, C. K., Epstein, J. N., Angold, A., & Klaric, J. (2003). Journal of Abnormal Child Psychology, 31(5), 555-562. doi:10.1023/a:1025457300409Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). «Mini-mental state». Journal of Psychiatric Research, 12(3), 189-198. doi:10.1016/0022-3956(75)90026-6Fordell, H., Bodin, K., Bucht, G., & Malm, J. (2011). A virtual reality test battery for assessment and screening of spatial neglect. Acta Neurologica Scandinavica, 123(3), 167-174. doi:10.1111/j.1600-0404.2010.01390.xGupta, V., Knott, B. A., Kodgi, S., & Lathan, C. E. (2000). Using the «VREye» System for the Assessment of Unilateral Visual Neglect: Two Case Reports. Presence: Teleoperators and Virtual Environments, 9(3), 268-286. doi:10.1162/105474600566790Hartman-Maeir, A., & Katz, N. (1995). Validity of the Behavioral Inattention Test (BIT): Relationships With Functional Tasks. American Journal of Occupational Therapy, 49(6), 507-516. doi:10.5014/ajot.49.6.507Jannink, M. J. A., Aznar, M., de Kort, A. C., van de Vis, W., Veltink, P., & van der Kooij, H. (2009). Assessment of visuospatial neglect in stroke patients using virtual reality: a pilot study. International Journal of Rehabilitation Research, 32(4), 280-286. doi:10.1097/mrr.0b013e3283013b1cJehkonen, M., Laihosalo, M., & Kettunen, J. (2006). Anosognosia after stroke: assessment, occurrence, subtypes and impact on functional outcome reviewed. Acta Neurologica Scandinavica, 114(5), 293-306. doi:10.1111/j.1600-0404.2006.00723.xKatz, N., Ring, H., Naveh, Y., Kizony, R., Feintuch, U., & Weiss, P. L. (2005). Interactive virtual environment training for safe street crossing of right hemisphere stroke patients with Unilateral Spatial Neglect. Disability and Rehabilitation, 27(20), 1235-1244. doi:10.1080/09638280500076079Kim, D. Y., Ku, J., Chang, W. H., Park, T. H., Lim, J. Y., Han, K., … Kim, S. I. (2010). Assessment of post-stroke extrapersonal neglect using a three-dimensional immersive virtual street crossing program. Acta Neurologica Scandinavica, 121(3), 171-177. doi:10.1111/j.1600-0404.2009.01194.xKim, J., Kim, K., Kim, D. Y., Chang, W. H., Park, C.-I., Ohn, S. H., … Kim, S. I. (2007). Virtual Environment Training System for Rehabilitation of Stroke Patients with Unilateral Neglect: Crossing the Virtual Street. CyberPsychology & Behavior, 10(1), 7-15. doi:10.1089/cpb.2006.9998Kim, K., Kim, J., Ku, J., Kim, D. Y., Chang, W. H., Shin, D. I., … Kim, S. I. (2004). A Virtual Reality Assessment and Training System for Unilateral Neglect. CyberPsychology & Behavior, 7(6), 742-749. doi:10.1089/cpb.2004.7.742Kim, Y. M., Chun, M. H., Yun, G. J., Song, Y. J., & Young, H. E. (2011). The Effect of Virtual Reality Training on Unilateral Spatial Neglect in Stroke Patients. Annals of Rehabilitation Medicine, 35(3), 309. doi:10.5535/arm.2011.35.3.309Krakauer, J. W. (2006). Motor learning: its relevance to stroke recovery and neurorehabilitation. Current Opinion in Neurology, 19(1), 84-90. doi:10.1097/01.wco.0000200544.29915.ccMcComas, J., MacKay, M., & Pivik, J. (2002). Effectiveness of Virtual Reality for Teaching Pedestrian Safety. CyberPsychology & Behavior, 5(3), 185-190. doi:10.1089/109493102760147150Myers, R. L., & Bierig, T. A. (2000). Virtual Reality and Left Hemineglect: A Technology for Assessment and Therapy. CyberPsychology & Behavior, 3(3), 465-468. doi:10.1089/10949310050078922Peskine, A., Rosso, C., Box, N., Galland, A., Caron, E., Rautureau, G., … Pradat-Diehl, P. (2010). Virtual reality assessment for visuospatial neglect: importance of a dynamic task. Journal of Neurology, Neurosurgery & Psychiatry, 82(12), 1407-1409. doi:10.1136/jnnp.2010.217513Romero, M., Sánchez, A., Marín, C., Navarro, M. D., Ferri, J., & Noé, E. (2012). Utilidad clínica de la versión en castellano del Mississippi Aphasia Screening Test (MASTsp): validación en pacientes con ictus. Neurología, 27(4), 216-224. doi:10.1016/j.nrl.2011.06.006Rose, F. D., Brooks, B. M., & Rizzo, A. A. (2005). Virtual Reality in Brain Damage Rehabilitation: Review. CyberPsychology & Behavior, 8(3), 241-262. doi:10.1089/cpb.2005.8.241Schwebel, D. C., & McClure, L. A. (2010). Using virtual reality to train children in safe street-crossing skills. Injury Prevention, 16(1), e1-e1. doi:10.1136/ip.2009.025288Simpson, G., Johnston, L., & Richardson, M. (2003). An investigation of road crossing in a virtual environment. Accident Analysis & Prevention, 35(5), 787-796. doi:10.1016/s0001-4575(02)00081-7Smith, J., Hebert, D., & Reid, D. (2007). Exploring the effects of virtual reality on unilateral neglect caused by stroke: Four case studies. Technology and Disability, 19(1), 29-40. doi:10.3233/tad-2007-19104Sugarman, H., Weisel-Eichler, A., Burstin, A. and Brown, R.Use of novel virtual reality system for the assessment and treatment of unilateral spatial neglect: A feasibility study. Paper presented at International Conference on Virtual Rehabilitation. Zürich.Tanaka, T., Sugihara, S., Nara, H., Ino, S., & Ifukube, T. (2005). Journal of NeuroEngineering and Rehabilitation, 2(1), 31. doi:10.1186/1743-0003-2-31Thomson, J. A., Tolmie, A. K., Foot, H. C., Whelan, K. M., Sarvary, P., & Morrison, S. (2005). Influence of Virtual Reality Training on the Roadside Crossing Judgments of Child Pedestrians. Journal of Experimental Psychology: Applied, 11(3), 175-186. doi:10.1037/1076-898x.11.3.175Weiss, P. L. (Tamar), Naveh, Y., & Katz, N. (2003). Design and testing of a virtual environment to train stroke patients with unilateral spatial neglect to cross a street safely. Occupational Therapy International, 10(1), 39-55. doi:10.1002/oti.176Witmer, B. G., & Singer, M. J. (1998). Measuring Presence in Virtual Environments: A Presence Questionnaire. Presence: Teleoperators and Virtual Environments, 7(3), 225-240. doi:10.1162/105474698565686Wu, H., Ashmead, D. H. and Bodenheimer, B.Using immersive virtual reality to evaluate pedestrian street crossing decisions at a roundabout. Paper presented at 6th Symposium on appied perception in Graphics and Visualization. Chania

The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C