Quantum dot encapsulation in virus-like particles with tuneable structural properties and low toxicity

A simple method for the encapsulation of quantum dots (QDs) in virus-like particle (VLP) nanoassemblies with tuneable structural properties and enhanced biocompatibility is presented. Cowpea chlorotic mottle virus-based capsid proteins assemble around the carboxylated QDs to form QD/VLP nanoassemblies of different capsid size as a function of pH and ionic strength. Detailed structural characterizations verify that nanoassemblies with probably native capsid icosahedral symmetry (T = 3) are obtained at low pH and high ionic strength (pH 5.0, 1.0 M NaCl), whereas high pH and low ionic strength conditions (pH 7.5, 0.3 M NaCl) result in the formation of smaller assembly sizes similar to T = 1 symmetry. In vitro studies reveal that QD/VLP nanoassemblies are efficiently internalized by RAW 264.7 macrophages and HeLa cells with no signs of toxicity at QD concentrations exceeding the potentially-toxic levels. The presented route holds great promise for preparation of size-tuneable, robust, non-toxic luminescent probes for long term cellular imaging applications. Furthermore, thanks to the possibility of chemical and genetic manipulation of the viral protein shell encaging the QDs, the nanoassemblies have potential for in vivo targeting applications

Conventionally assessed voluntary activation does not represent relative voluntary torque production

The ability to voluntarily activate a muscle is commonly assessed by some variant of the twitch interpolation technique (ITT), which assumes that the stimulated force increment decreases linearly as voluntary force increases. In the present study, subjects (n = 7) with exceptional ability for maximal voluntary activation (VA) of the knee extensors were used to study the relationship between superimposed and voluntary torque. This includes very high contraction intensities (90–100%VA), which are difficult to consistently obtain in regular healthy subjects (VA of ∼90%). Subjects were tested at 30, 60, and 90° knee angles on two experimental days. At each angle, isometric knee extensions were performed with supramaximal superimposed nerve stimulation (triplet: three pulses at 300 Hz). Surface EMG signals were obtained from rectus femoris, vastus lateralis, and medialis muscles. Maximal VA was similar and very high across knee angles: 97 ± 2.3% (mean ± SD). At high contraction intensities, the increase in voluntary torque was far greater than would be expected based on the decrement of superimposed torque. When voluntary torque increased from 79.6 ± 6.1 to 100%MVC, superimposed torque decreased from 8.5 ± 2.6 to 2.8 ± 2.3% of resting triplet. Therefore, an increase in VA of 5.7% (from 91.5 ± 2.6 to 97 ± 2.3%) coincided with a much larger increase in voluntary torque (20.4 ± 6.1%MVC) and EMG (33.9 ± 6.6%max). Moreover, a conventionally assessed VA of 91.5 ± 2.6% represented a voluntary torque of only 79.6 ± 6.1%MVC. In conclusion, when maximal VA is calculated to be ∼90% (as in regular healthy subjects), this probably represents a considerable overestimation of the subjects’ ability to maximally drive their quadriceps muscles

The feasibility of whole body vibration in institutionalised elderly persons and its influence on muscle performance, balance and mobility: a randomised controlled trial [ISRCTN62535013]

BACKGROUND: Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents. Low-volume exercise interventions with similar training effects might be an alternative. The aim of this randomised controlled trial was to investigate the feasibility of Whole Body Vibration (WBV) in institutionalised elderly, and its impact on functional capacity and muscle performance. METHODS: Twenty-four nursing home residents (15 female, 9 male; mean age 77.5 ± 11.0 years) were randomised (stratification for age, gender and ADL-category) to 6 weeks static WBV exercise (WBV+, N = 13) or control (only static exercise; N = 11). Outcome measures were exercise compliance, timed up-and-go, Tinetti-test, back scratch, chair sit-and-reach, handgrip strength and linear isokinetic leg extension. RESULTS: At baseline, WBV+ and control groups were similar for all outcome variables. Twenty-one participants completed the program and attended respectively 96% and 86% of the exercise sessions for the WBV+ and control groups. Training-induced changes in timed up-and-go and Tinetti-test were better for WBV+ compared to control (p = 0.029 for timed up-and-go, p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively). In an alternative analysis (Worst Rank Score & Last Observation Carried Forward) the differences in change remained significant on the Tinetti body balance and total score. No other significant differences in change between both groups were observed. CONCLUSION: In nursing home residents with limited functional dependency, six weeks static WBV exercise is feasible, and is beneficial for balance and mobility. The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further

Tumor heterogeneity in neoplasms of breast, colon, and skin

<p>Abstract</p> <p>Background</p> <p>Different cell subpopulations in a single tumor may show diverse capacities for growth, differentiation, metastasis formation, and sensitivity to treatments. Thus, heterogeneity is an important feature of tumors. However, due to limitations in experimental and analytical techniques, tumor heterogeneity has rarely been studied in detail.</p> <p>Presentation of the hypothesis</p> <p>Different tumor types have different heterogeneity patterns, thus heterogeneity could be a characteristic feature of a particular tumor type.</p> <p>Testing the hypothesis</p> <p>We applied our previously published mathematical heterogeneity model to decipher tumor heterogeneity through the analysis of genetic copy number aberrations revealed by array CGH data for tumors of three different tissues: breast, colon, and skin. The model estimates the number of subpopulations present in each tumor. The analysis confirms that different tumor types have different heterogeneity patterns. Computationally derived genomic copy number profiles from each subpopulation have also been analyzed and discussed with reference to the multiple hypothetical relationships between subpopulations in origin-related samples.</p> <p>Implications of the hypothesis</p> <p>Our observations imply that tumor heterogeneity could be seen as an independent parameter for determining the characteristics of tumors. In the context of more comprehensive usage of array CGH or genome sequencing in a clinical setting our study provides a new way to realize the full potential of tumor genetic analysis.</p

Intermodal attention affects the processing of the temporal alignment of audiovisual stimuli

The temporal asynchrony between inputs to different sensory modalities has been shown to be a critical factor influencing the interaction between such inputs. We used scalp-recorded event-related potentials (ERPs) to investigate the effects of attention on the processing of audiovisual multisensory stimuli as the temporal asynchrony between the auditory and visual inputs varied across the audiovisual integration window (i.e., up to 125 ms). Randomized streams of unisensory auditory stimuli, unisensory visual stimuli, and audiovisual stimuli (consisting of the temporally proximal presentation of the visual and auditory stimulus components) were presented centrally while participants attended to either the auditory or the visual modality to detect occasional target stimuli in that modality. ERPs elicited by each of the contributing sensory modalities were extracted by signal processing techniques from the combined ERP waveforms elicited by the multisensory stimuli. This was done for each of the five different 50-ms subranges of stimulus onset asynchrony (SOA: e.g., V precedes A by 125–75 ms, by 75–25 ms, etc.). The extracted ERPs for the visual inputs of the multisensory stimuli were compared among each other and with the ERPs to the unisensory visual control stimuli, separately when attention was directed to the visual or to the auditory modality. The results showed that the attention effects on the right-hemisphere visual P1 was largest when auditory and visual stimuli were temporally aligned. In contrast, the N1 attention effect was smallest at this latency, suggesting that attention may play a role in the processing of the relative temporal alignment of the constituent parts of multisensory stimuli. At longer latencies an occipital selection negativity for the attended versus unattended visual stimuli was also observed, but this effect did not vary as a function of SOA, suggesting that by that latency a stable representation of the auditory and visual stimulus components has been established