Varietal differences in protein polymer built-up of wheat at different temperature and nitrogen regimes during grain filling

Both radionuclide imaging and near-infrared fluorescent (NIRF) imaging have a high sensitivity to detect tumors in vivo. The combination of these modalities using dual-labeled antibodies may allow both preoperative and intraoperative tumor localization and may be used in image-guided surgery to ensure complete resection of tumor tissue. Here, we evaluated the potential of dual-modality imaging of prostate cancer with the monoclonal antibody D2B, directed against an extracellular domain of prostate-specific membrane antigen (PSMA). For these studies, D2B was labeled both with (111)In and with the NIRF dye IRDye800CW.D2B was conjugated with N-hydroxysuccinimide-IRDye800CW and p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (ITC-DTPA) and subsequently radiolabeled with (111)In. For biodistribution and NIRF imaging, (111)In-DTPA-D2B-IRDye800CW (2 μg, 0.55 MBq/mouse) was injected intravenously into BALB/c nude mice with subcutaneous PSMA-expressing LNCaP tumors (right flank) and PSMA-negative PC3 tumors (left flank). The biodistribution was determined at 1, 2, 3, and 7 d after injection. In addition, micro-SPECT/CT and NIRF imaging with (111)In-DTPA-D2B-IRDye800CW (3 μg, 8.5 MBq/mouse) was performed on mice with intraperitoneally growing LS174T-PSMA tumors.(111)In-DTPA-D2B-IRDye800CW specifically accumulated in subcutaneous PSMA-positive LNCaP tumors (45.8 ± 8.0 percentage injected dose per gram at 168 h after injection), whereas uptake in subcutaneous PSMA-negative PC3 tumors was significantly lower (6.6 ± 1.3 percentage injected dose per gram at 168 h after injection). Intraperitoneal LS174T-PSMA tumors could be visualized specifically with both micro-SPECT/CT and NIRF imaging at 2 d after injection, and the feasibility of image-guided resection of intraperitoneal tumors was demonstrated in this model.Dual-labeled (111)In-DTPA-D2B-IRDye800CW enables specific and sensitive detection of prostate cancer lesions in vivo with micro-SPECT/CT and NIRF imaging. In addition to preoperative micro-SPECT/CT imaging to detect tumors, NIRF imaging enables image-guided surgical resection. These preclinical findings warrant clinical studies with (111)In-DTPA-D2B-IRDye800CW to improve tumor detection and resection in prostate cancer patients

Participant music listening behaviours in interactive multimedia music instruction

While emerging technologies such as interactive multimedia are increasingly being employed in computerised music instruction, understanding of participant music listening behaviours in interactive multimedia music instruction is currently very limited. With the aim of elucidating music listening behaviour, the central concern of this work is to identify and explain participant interactions with the audio components of interactive multimedia music instruction. The investigation employs a novel documentation procedure, which extends the application of digital audio recording technology, to provide a finely calibrated analysis of the audio activity of a sample of 20 undergraduate music education majors during individual sessions with two commercially-available interactive multimedia music instruction programs. Graphically-based Sound Activity Profiles, which the researcher developed specifically for the current investigation, characterise and summarise participant interactions with audio components, while an analysis of questionnaire responses and follow-up interview transcripts provides supplementary information that further explains participants' music listening behaviours. The results of the investigation show that music listening behaviours during the study sessions were highly variable. While extensive participant interaction with music examples occasionally reflected attentive music listening behaviours, many study sessions were characterised by brief, fragmentary music excerpts and lengthy periods of silence. Participants spent as little as five percent of their session time listening to music and as much as 88 percent of the session time in silence. A substantial number of the study cohort frequently interrupted the music examples they had activated. Participants' perceptions of the extent of their interaction with music examples were frequently inaccurate, as subjects often substantially overestimated the amount of session time they had spent listening to music. The study findings suggest that many interactive multimedia music instruction participants would benefit from interventions that elicit more extensive and prolonged interaction with music examples. Accordingly, recommendations include a call for research to develop and test software designs that incorporate automated monitoring of session audio activity so that dynamic on-screen information about music listening behaviour can be provided to interactive multimedia music instruction participants. Such information may encourage participants to modify inappropriate music listening behaviours

FROM MOUSTACHES TO MY SPACES

Radical removal of malignant lesions may be improved using tumor-targeted dual-modality probes that contain both a radiotracer and a fluorescent label to allow for enhanced intraoperative delineation of tumor resection margins. Because pretargeting strategies yield high signal-to-background ratios, we evaluated the feasibility of a pretargeting strategy for intraoperative imaging in prostate cancer using an anti-TROP-2 x anti-HSG bispecific antibody (TF12) in conjunction with the dual-labeled diHSG peptide (RDC018) equipped with both a DOTA chelate for radiolabeling purposes and a fluorophore (IRdye800CW) to allow near-infrared optical imaging. Nude mice implanted s.c. with TROP-2-expressing PC3 human prostate tumor cells or with PC3 metastases in the scapular and suprarenal region were injected i.v. with 1 mg of TF12 and, after 16 hours of tumor accumulation and blood clearance, were subsequently injected with 10 MBq, 0.2 nmol/mouse of either (111)In-RDC018 or (111)In-IMP288 as a control. Two hours after injection, both microSPECT/CT and fluorescence images were acquired, both before and after resection of the tumor nodules. After image acquisition, the biodistribution of (111)In-RDC018 and (111)In-IMP288 was determined and tumors were analyzed immunohistochemically. The biodistribution of the dual-label RDC018 showed specific accumulation in the TROP-2-expressing PC3 tumors (12.4 +/- 3.7% ID/g at 2 hours postinjection), comparable with (111)In-IMP288 (9.1 +/- 2.8% ID/g at 2 hours postinjection). MicroSPECT/CT and near-infrared fluorescence (NIRF) imaging confirmed this TROP-2-specific uptake of the dual-label (111)In-RDC018 in both the s.c. and metastatic growing tumor model. In addition, PC3 metastases could be visualized preoperatively with SPECT/CT and could subsequently be resected by image-guided surgery using intraoperative NIRF imaging, showing the preclinical feasibility of pretargeted dual-modality imaging approach in prostate cancer

Hippocampal involvement in associative working memory: Evidence from fMRI

Contains fulltext : 77035.pdf (publisher's version ) (Open Access)1 p

The hippocampus supports encoding of between-domain associations within working memory

Contains fulltext : 77282.pdf (publisher's version ) (Open Access)It has been established that the medial temporal lobe, including the hippocampus, is crucial for associative memory. The aim of the current functional magnetic resonance imaging (fMRI) study was to investigate whether the hippocampus is differentially activated for associations between items processed in the same neocortical region (within-domain) as compared with associations between items processed in different neocortical regions (between-domain). Here, we show that the hippocampus is significantly more active for between-domain associations compared with within-domain associations. Thus, the hippocampus is important for associative encoding, and furthermore, shows greater activation when the stimuli to be associated come from different stimulus categories.4 p

BDNF Val66Met polymorphism interacts with sex to influence bimanual motor control in healthy humans

Contains fulltext : 110357.pdf (publisher's version ) (Open Access)Brain-derived neurotrophic factor (BDNF) plays a critical role in brain development. A common single nucleotide polymorphism in the gene encoding BDNF (rs6265, Val66Met) affects BDNF release and has been associated with altered learning and memory performance, and with structural changes in brain morphology and corpus callosum integrity. BDNF Val66Met has more recently been shown to influence motor learning and performance. Some of the BDNF effects seem to be modulated by an individual's sex, but currently the relationship between BDNF and sex in the motor domain remains elusive. Here, we investigate the relationship between BDNF Val66Met genotype and an individual's sex in the motor system. Seventy-six healthy, previously genotyped, individuals performed a task in which the participant drew lines at different angles of varying difficulty. Subjects controlled the horizontal and vertical movement of the line on a computer screen by rotating two cylinders. We used this bimanual motor control task to measure contributions from both current motor function and the pre-existing interhemispheric connectivity. We report that BDNF genotype interacts with sex to influence the motor performance of healthy participants in this bimanual motor control task. We further report that the BDNF genotype by sex interaction was present in the more difficult trials only, which is in line with earlier findings that genetic effects may become apparent only when a system is challenged. Our results emphasize the importance of taking sex into account when investigating the role of BDNF genotype in the motor system

Retrieval of associative information congruent with prior knowledge is related to increased medial prefrontal activity and connectivity.

Contains fulltext : 89374.pdf (publisher's version ) (Open Access)We remember information that is congruent instead of incongruent with prior knowledge better, but the underlying neural mechanisms related to this enhancement are still relatively unknown. Recently, this memory enhancement due to a prior schema has been suggested to be based on rapid neocortical assimilation of new information, related to optimized encoding and consolidation processes. The medial prefrontal cortex (mPFC) is thought to be important in mediating this process, but its role in retrieval of schema-consistent information is still unclear. In this study, we regarded multisensory congruency with prior knowledge as a schema and used this factor to probe retrieval of consolidated memories either consistent or inconsistent with prior knowledge. We conducted a visuotactile learning paradigm in which participants studied visual motifs randomly associated with word-fabric combinations that were either congruent or incongruent with common knowledge. The next day, participants were scanned using functional magnetic resonance imaging while their memory was tested. Congruent associations were remembered better than incongruent ones. This behavioral finding was parallelized by stronger retrieval-related activity in and connectivity between medial prefrontal and left somatosensory cortex. Moreover, we found a positive across-subject correlation between the connectivity enhancement and the behavioral congruency effect. These results show that successful retrieval of congruent compared to incongruent visuotactile associations is related to enhanced processing in an mPFC-somatosensory network, and support the hypothesis that new information that fits a preexisting schema is more rapidly assimilated in neocortical networks, a process that may be mediated, at least in part, by the mPFC

Consolidation differentially modulates schema effects on memory for items and associations

Contains fulltext : 115381.pdf (publisher's version ) (Open Access)Newly learned information that is congruent with a preexisting schema is often better remembered than information that is incongruent. This schema effect on memory has previously been associated to more efficient encoding and consolidation mechanisms. However, this effect is not always consistently supported in the literature, with differential schema effects reported for different types of memory, different retrieval cues, and the possibility of time-dependent effects related to consolidation processes. To examine these effects more directly, we tested participants on two different types of memory (item recognition and associative memory) for newly encoded visuo-tactile associations at different study-test intervals, thus probing memory retrieval accuracy for schema-congruent and schema-incongruent items and associations at different time points (t = 0, t = 20, and t = 48 hours) after encoding. Results show that the schema effect on visual item recognition only arises after consolidation, while the schema effect on associative memory is already apparent immediately after encoding, persisting, but getting smaller over time. These findings give further insight into different factors influencing the schema effect on memory, and can inform future schema experiments by illustrating the value of considering effects of memory type and consolidation on schema-modulated retrieval

Tumor Targeting using Radiolabeled Antibodies for Image-Guided Drug Delivery

Item does not contain fulltextDue to their high target affinity and specificity, antibodies are very suitable tumor-targeting vehicles for imaging and therapeutic application. This enables a theranostic approach of imaging targeted drug delivery in oncology and opens the way for personalized medicine, predicting drug delivery, response, and treatment outcome in the individual patient. Of the currently available molecular imaging techniques, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are the best suited imaging techniques to visualize and determine drug delivery to the target tissue quantitatively. Using the same antibody for imaging and targeted therapy may eliminate some limitations of antibody-based molecular imaging and therapy, like heterogeneous antigen expression and poor accessibility. However, challenges of this approach remain, for example in the pharmacokinetic behavior of radiolabeled antibodies and antibody-drug-conjugates. Despite these challenges, also exciting opportunities are at the horizon, by using antibodies as multimodal vehicles carrying both a diagnostic agent and a therapeutic agent. In this review, both the challenges and the opportunities of using radiolabeled antibodies for image-guided drug delivery are discussed