A translation proofreader of archaeal origin imparts multi-aldehyde stress tolerance to land plants.

Aldehydes, being an integral part of carbon metabolism, energy generation, and signalling pathways, are ingrained in plant physiology. Land plants have developed intricate metabolic pathways which involve production of reactive aldehydes and its detoxification to survive harsh terrestrial environments. Here, we show that physiologically produced aldehydes, i.e., formaldehyde and methylglyoxal in addition to acetaldehyde, generate adducts with aminoacyl-tRNAs, a substrate for protein synthesis. Plants are unique in possessing two distinct chiral proofreading systems, D-aminoacyl-tRNA deacylase1 (DTD1) and DTD2, of bacterial and archaeal origins, respectively. Extensive biochemical analysis revealed that only archaeal DTD2 can remove the stable D-aminoacyl adducts on tRNA thereby shielding archaea and plants from these system-generated aldehydes. Using Arabidopsis as a model system, we have shown that the loss of DTD2 gene renders plants susceptible to these toxic aldehydes as they generate stable alkyl modification on D-aminoacyl-tRNAs, which are recycled only by DTD2. Bioinformatic analysis identifies the expansion of aldehyde metabolising repertoire in land plant ancestors which strongly correlates with the recruitment of archaeal DTD2. Finally, we demonstrate that the overexpression of DTD2 offers better protection against aldehydes than in wild type Arabidopsis highlighting its role as a multi-aldehyde detoxifier that can be explored as a transgenic crop development strategy.

Nano-modified screen-printed electrode-based electrochemical immunosensors for oral cancer biomarker detection in undiluted human serum and saliva samples.

This proposed work reports the development of in-house made conductive ink-based screen-printed electrodes (SPEs) for label-free detection of oral cancer biomarkers. Carbon ink synthesis includes graphite powder, gum arabic, and water. The selectivity test of the fabricated SPE involves immobilizing antibodies specific to biomarkers and challenges with redox-active interference, other serum molecules, and non-target biomarkers. Three different biomarkers, cytokeratin-19 fragment (CYFRA 21-1), interleukin 8 (IL-8), and tumor protein p53 (TP-53), act as target entities for the detection of oral cancer in patients' samples (serum, N = 28, and saliva, N = 16) at an early stage. The standard technique enzyme-linked immunosorbent assay (ELISA) was employed to estimate the concentration of the biomarkers in serum and saliva samples. SPEs contain amine (-NH2) functional groups involved in covalent bonding with the carboxyl (-COOH) groups of antibody molecules. These immunosensors exhibited remarkably lower detection limits of 829.5 pg mL-1, 0.543 pg mL-1, and 1.165 pg mL-1, and excellent sensitivity of 0.935 µA mL pg-1 cm-1, 0.039 µA mL pg-1 cm-1, and 0.008 µA mL pg-1 cm-1 for CYFRA 21-1, IL-8, and TP-53 biomarkers, respectively. This sensing platform does not require any functionalization for biomolecule immobilization. Thus, it is a cost-effective, disposable, flexible, miniaturized, and sensitive strip to detect oral cancer biomarkers.

Investigation of Luliconazole-Loaded Mucoadhesive Electrospun Nanofibers for Anticandidal Activity in the Management of Vaginal Candidiasis.

In this study, we fabricated and evaluated luliconazole-loaded electrospun nanofibers for anticandidal activity in the management of vaginal candidiasis. Polycaprolactone (PCL)/gelatin nanofibers were designed by the electrospinning technique, and the Box-Behnken design (BBD) was adopted for optimization to get tailored fibers. The luliconazole (LCZ) drug was mixed into different concentrations (2.5, 5, 7.5, and 10%) of tea tree oil (TT oil) and loaded into the PCL/gelatin nanofibrous mats. The effective anticandidal potential of nanofiber samples were analyzed by the disk-diffusion method. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), XRD analysis, and in silico study were performed. The entrapment efficiency, swelling degree, mechanical strength, contact angle, mucoadhesion, drug release, and permeation study were assessed. The average diameter of the PCL/gelatin-optimized nanofiber was 153 nm. SEM reflected that the fabricated nanofibers were uniform and bead-free. FTIR and DSC analyzed the interaction and physical entrapment of the drug in the polymeric fibers. The entrapment efficiency of the drug-loaded nanofiber was found to be 89.2 ± 0.8%. Maximum swelling percentages at 4 h were 40.8, 18.9, and 14.0% and contact angles were 46.5°, 62.95°, and 65.78° for the blank, TT oil-loaded, and drug-loaded nanofiber, respectively, which indicated the hydrophilic nature of the fibers. The drug-loaded nanofiber had a high tensile strength with satisfactory mucoadhesive property that led to its adhesion to the vaginal mucosa with no tear. The drug-loaded nanofiber had a cumulative drug release of 67.7 ± 3.4% in 48 h, and the 12.8 ± 0.53 mm of zone of inhibition (ZOI) in 48 h illustrated an effective anticandidal activity. The TT oil-loaded nanofiber also exhibited a small ZOI of 4.3 ± 0.30 mm, indicating a synergistic effect to the antifungal activity of the drug-loaded nanofiber. LCZ-loaded nanofibers can emerge as a novel approach for vaginal drug delivery in the treatment of candida infection. Thus, this pharmaceutical investigation can help in formulating preclinical and clinical models.

Calcium-assisted sortase A cleavage of SUMOylated metallothionein constructs leads to high-yield production of human MT3.

BACKGROUND: Mammalian metallothioneins (MTs) are small (6-7 kDa), intracellular, cysteine-rich, metal-binding proteins involved, inter alia, in the homeostasis of zinc and copper, detoxification of heavy metals, antioxidation against reactive oxygen species, and protection against DNA damage. The high cysteine content (~ 30%) in MTs makes them toxic to bacterial cells during protein production, resulting in low yield. To address this issue, we present for the first time a combinatorial approach using the small ubiquitin-like modifier (SUMO) and/or sortase as fusion tags for high-level expression of human MT3 in E. coli and its purification by three different strategies. RESULTS: Three different plasmids were generated using SUMO, sortase A pentamutant (eSrtA), and sortase recognition motif (LPETG) as removable fusion tags for high-level expression and purification of human MT3 from the bacterial system. In the first strategy, SUMOylated MT3 was expressed and purified using Ulp1-mediated cleavage. In the second strategy, SUMOylated MT3 with a sortase recognition motif at the N-terminus of MT3 was expressed and purified using sortase-mediated cleavage. In the final strategy, the fusion protein His6-SUMO-eSrtA-LPETG-MT3 was expressed and purified by one-step sortase-mediated inducible on-bead autocleavage. Using these three strategies the apo-MT3 was purified in a yield of 11.5, 11, and 10.8 mg/L, respectively, which is the highest yield achieved for MT expression and purification to date. No effect of MT3 on Ni2+-containing resin was observed. CONCLUSION: The SUMO/sortase-based strategy used as the production system for MT3 resulted in a very high expression level and protein production yield. The apo-MT3 purified by this strategy contained an additional glycine residue and had similar metal binding properties as WT-MT3. This SUMO-sortase fusion system is a simple, robust, and inexpensive one-step purification approach for various MTs as well as other toxic proteins with very high yield via immobilized metal affinity chromatography (IMAC).

Graphene oxide-Mn3O4nanocomposites for advanced electrochemical biosensor for fumonisin B1 detection.

Occurrence of mycotoxins in food samples threat to its safety issue due to the presence of high toxicity and carcinogenic behavior, thus requiring highly sensitive and selective detection. Herein, the trimanganese tetraoxide (Mn3O4) nanoparticles in combination with graphene oxide (GO) nanocomposite were used to enhance the electrochemical performance for fabrication of electrochemical biosensor for fumonisin B1 (FB1) detection. The various characterization tools were used to validate the fabrication of GOMn3O4nanocomposites. To fabricate the electrochemical biosensor on an indium tin oxide (ITO) coated glass substrate, a thin film of GOMn3O4nanocomposite was prepared using electrophoretic deposition technique, and antibodies (ab-FB1) were immobilized onto the electrode for selective FB1 detection. The differential pulse voltammetry technique was used to observe the sensing performance. The non-binding sites of the ab-FB1 on the immunoelectrode were blocked with bovine serum albumin (BSA). The biosensor electrode was fabricated as BSA/ab-FB1/GOMn3O4/ITO for the detection of FB1. The sensitivity of the biosensor was obtained as 10.08µA ml ng-1cm-2in the detection range of 1 pg ml-1to 800 ng ml-1with a limit of detection of 0.195 pg ml-1. In addition, the recovery of BSA/ab-FB1/GOMn3O4/ITO immunoelectrodes was also performed on sweet corn samples and is calculated to be 98.91%.

Distinct localization of chiral proofreaders resolves organellar translation conflict in plants.

Plants have two endosymbiotic organelles originated from two bacterial ancestors. The transition from an independent bacterium to a successful organelle would have required extensive rewiring of biochemical networks for its integration with archaeal host. Here, using Arabidopsis as a model system, we show that plant D-aminoacyl-tRNA deacylase 1 (DTD1), of bacterial origin, is detrimental to organellar protein synthesis owing to its changed tRNA recognition code. Plants survive this conflict by spatially restricting the conflicted DTD1 to the cytosol. In addition, plants have targeted archaeal DTD2 to both the organelles as it is compatible with their translation machinery due to its strict D-chiral specificity and lack of tRNA determinants. Intriguingly, plants have confined bacterial-derived DTD1 to work in archaeal-derived cytosolic compartment whereas archaeal DTD2 is targeted to bacterial-derived organelles. Overall, the study provides a remarkable example of the criticality of optimization of biochemical networks for survival and evolution of plant mitochondria and chloroplast.

A Screening Approach for Inherited Erythrocytosis due to the VHL:c.598C > T Mutation (Chuvash Polycythemia).

Genetic work-up of unexplained erythrocytosis that is suspected to be inherited in nature currently requires either laborious exon-by-exon gene panel testing by Sanger sequencing or expensive next-generation sequencing. A high prevalence of Chuvash polycythemia (61%) has been previously reported among north Indian erythrocytosis patients. We assessed PCR-RFLP for VHL c.598C > T mutation as a first-line test in 99 persons with JAK2 V617F-negative, unexplained erythrocytosis. We enrolled two groups: Group A (n = 38) had erythrocytosis patients (n = 33) or their first-degree relatives (n = 5), and, Group B with 61 healthy blood donation volunteers who were deferred after the discovery of unexplained high hemoglobin levels. Detailed history and clinical examination, hemogram, erythropoietin levels and PCR-RFLP for the VHL:c.598C > T;p.R200W mutation were done. In Group A, three (8%) persons aged 9, 13 and 30-years were homozygous for VHL:c.598C > T. Two were heterozygous (parents of a known case of Chuvash polycythemia). None of the Group B subjects had the Chuvash mutation. Erythropoietin levels in group A were low in 5/26 cases (19%) and normal in 18/26 (69%). In Group B, seven (11%) donors had normal values while the remaining 54 (89%) had high erythropoietin levels. Despite a lower frequency (8%) compared to literature, our results suggest that the relatively simpler PCR-RFLP for VHL:c.598C > T mutation may be considered for the initial genetic screening of unexplained, suspected congenital erythrocytosis in regions where Chuvash polycythemia comprises a large proportion of inherited erythrocytosis, after polycythemia vera and common acquired secondary causes are excluded. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01668-9.

The connection of α- and ß-domains in mammalian metallothionein-2 differentiates Zn(II) binding affinities, affects folding, and determines zinc buffering properties.

Mammalian metallothioneins (MTs) are small Cys-rich proteins involved in Zn(II) and Cu(I) homeostasis. They bind seven Zn(II) ions in two distinct ß- and α-domains, forming Zn3Cys9 and Zn4Cys11 clusters, respectively. After six decades of research, their role in cellular buffering of Zn(II) ions has begun to be understood recently. This is because of different affinities of bound ions and the proteins' coexistence in variously Zn(II)-loaded Zn4-7MT species in the cell. To date, it has remained unclear how these mechanisms of action occur and how the affinities are differentiated despite the Zn(S-Cys)4 coordination environment being the same. Here, we dissect the molecular basis of these phenomena by using several MT2 mutants, hybrid protein, and isolated domains. Through a combination of spectroscopic and stability studies, thiol(ate) reactivity, and steered molecular dynamics, we demonstrate that both protein folding and thermodynamics of Zn(II) ion (un)binding significantly differ between isolated domains and the whole protein. Close proximity reduces the degrees of freedom of separated domains, making them less dynamic. It is caused by the formation of intra- and interdomain electrostatic interactions. The energetic consequence of domains connection has a critical impact on the role of MTs in the cellular environment, where they function not only as a zinc sponge but also as a zinc buffering system keeping free Zn(II) in the right concentrations. Any change of that subtle system affects the folding mechanism, zinc site stabilities, and cellular zinc buffer components.

Effect of Imatinib treatment on renal anaemia in chronic myeloid leukemia patients.

PURPOSE: In this study, we investigate renal function and anaemia during imatinib treatment in patients with chronic myeloid leukaemia. METHODS: The patients with chronic myeloid leukaemia with chronic phase who had been treated with only imatinib for 12 months at Rajiv Gandhi Cancer Institute and Research Centre (New Delhi, India) were enrolled and prospectively analysed. The chronic renal impairment parameters, including estimated glomerular filtration rate and haemoglobin levels for anaemia from June 2020 to June 2022, were monitored in newly diagnosed in patients with chronic myeloid leukaemia-chronic phase. The data were analysed by SPSS software version 22. RESULTS: In total 55 patients with chronic myeloid leukaemia chronic phase who had been on imatinib for 12 months were monitored. The mean estimated glomerular filtration rate was significantly decreased (74 ± 14 to 59 ± 12 mL/min/1.73m2, p < 0.001) with a decrease in mean haemoglobin levels after 12 months (10.9 ± 2.01 to 9.0 ± 1.02, p < 0.004). The decreased estimated glomerular filtration rate was negatively correlated with haemoglobin levels after 1 year of imatinib administration (correlation coefficient = 0.892, R2 = 0.7976, p < 0.05). CONCLUSION: We recommended close monitoring of renal function and haemoglobin levels in patients with chronic myeloid leukaemia patients.

OaAEP1 Ligase-Assisted Chemoenzymatic Synthesis of Full Cysteine-Rich Metal-Binding Cyanobacterial Metallothionein SmtA.

Among all approaches used for the semisynthesis of natural or chemically modified products, enzyme-assisted ligation is among the most promising and dynamically developing approaches. Applying an efficient C247A mutant of Oldenlandia affinis plant ligase OaAEP1 and solid-phase peptide synthesis chemistry, we present the chemoenzymatic synthesis of a complete sequence of the cysteine-rich and metal-binding cyanobacterial metallothionein Synechococcus metallothionein A (SmtA). Zn(II) and Cd(II) binding to the newly synthesized SmtA showed identical properties to the protein expressed in Escherichia coli. The presented approach is the first example of the use of OaAEP1 mutant for total protein synthesis of metallothionein, which occurs in mild conditions preventing cysteine thiol oxidation. The recognition motif of the applied enzyme could naturally occur in the protein structure or be synthetically or genetically incorporated in some loops or secondary structure elements. Therefore, we envision that this strategy can be used for efficiently obtaining SmtA and for a wide range of proteins and their derivatives.

The FANCC-FANCE-FANCF complex is evolutionarily conserved and regulates meiotic recombination.

At meiosis, programmed meiotic DNA double-strand breaks are repaired via homologous recombination, resulting in crossovers (COs). From a large excess of DNA double-strand breaks that are formed, only a small proportion gets converted into COs because of active mechanisms that restrict CO formation. The Fanconi anemia (FA) complex proteins AtFANCM, MHF1 and MHF2 were previously identified in a genetic screen as anti-CO factors that function during meiosis in Arabidopsis thaliana. Here, pursuing the same screen, we identify FANCC as a new anti-CO gene. FANCC was previously only identified in mammals because of low primary sequence conservation. We show that FANCC, and its physical interaction with FANCE-FANCF, is conserved from vertebrates to plants. Further, we show that FANCC, together with its subcomplex partners FANCE and FANCF, regulates meiotic recombination. Mutations of any of these three genes partially rescues CO-defective mutants, which is particularly marked in female meiosis. Functional loss of FANCC, FANCE, or FANCF results in synthetic meiotic catastrophe with the pro-CO factor MUS81. This work reveals that FANCC is conserved outside mammals and has an anti-CO role during meiosis together with FANCE and FANCF.

The Fanconi Anemia (FA) pathway is the subject of intense interest owing to the role of FA as a tumor suppressor. Three FA complex proteins, FANCM, MHF1 and MHF2, were identified as factors that suppress crossover during meiosis in the model plant Arabidopsis thaliana. Here, the authors extended these findings and identified a novel anti-crossover factor and showed that it encodes the plant FANCC homolog, which was previously thought to be vertebrate-specific. They further showed that FANCC regulates meiotic crossover together with two other FA proteins, FANCE and FANCF. This suggests that the FANCC­E­F subcomplex was already regulating DNA repair in the common ancestor of all living eukaryotes.

Prevalence of Anemia among Chronic Myeloid Leukemia Patients Treated with Imatinib: A Evidence-based Meta-analysis.

BACKGROUND: Imatinib is one of the tyrosine kinase inhibitors used for the treatment of chronic myeloid leukemia (CML) patients. The exact association of imatinib with anemia in CML patients is still unclear. AIM: The current study aimed to find the prevalence of anemia in chronic myeloid leukemia patients treated with imatinib. METHODS: The relevant articles were searched in PubMed, Google scholar, and Clinical trials registries till 31st July, 2021. The quality of the articles was assessed using the Newcastle-Ottawa Scale. The prevalence rate with 95% CI was calculated using StatsDirect Statistical analysis software V.3. RESULTS: A total of 18 studies containing 3537 patients were found relevant for the analysis. The pooled prevalence of anemia in CML was found to be 34% (95% CI: 23%-46%). However, the heterogeneity among studies was found to be high. CONCLUSION: The monitoring of hemoglobin levels and identifying the cause of anemia are major concerns for the CML patients treated with Imatinib.

Spectroscopic investigation on the interaction of direct yellow-27 with protein (BSA).

Direct yellow 27 (DY-27) interaction with bovine serum albumin (BSA) was investigated using multi-spectroscopic techniques to understand the toxicity mechanism. Fluorescence quenching of BSA by DY-27 was observed as a result of the formation of a BSA-DY27 complex with a binding constant of 1.19 × 105M-1and followed a static quenching mechanism with a quenching constant Ksvof 7.25 × 104M-1. The far UV circular dichroism spectra revealed the conformational changes in the secondary structure of BSA in the presence of DY-27. The calculated average lifetime of BSA is 6.04 ns and is nearly constant (5.99 ns) in the presence of dye and supports the proposed quenching mechanism. The change in free energy (ΔG) was calculated to be -28.96 kJ mol-1and confirmed the spontaneity of the binding process. Further, docking studies have been conducted to gain more insights into the interactions between DY-27 and serum albumin.

Predicting the Quality of Spatial Learning via Virtual Global Landmarks.

Analyzing the effects landmarks have on spatial learning is an active area of research in the study of human navigation processes and one that is key to understanding the links between human brain dynamics, landmark encoding, and spatial learning outcomes. This article presents a study on whether electroencephalography (EEG) signals related to virtual global landmarks combined with deep learning can be used to predict the accuracy and efficacy of spatial learning. Virtual global landmarks are silhouettes of actual landmarks projected into the navigator's vision via a heads-up display. They serve as a notable frame of reference in addition to the local landmarks we all typically use for route navigation. From a mobile virtual reality scenario involving 55 participants, the results of the study suggest that the EEG data associated with those who were exposed to global landmarks shows a visibly better capacity for predicting the quality of spatial learning levels than those who were not. As such, the EEG features associated with processing VGLs have a greater functional relation to the quality of spatial learning. This finding opens up a future direction of enquiry into landmark encoding and navigational ability. It may also provide a potential avenue for the early diagnosis of Alzheimer's disease.

Role of colchicine in the management of COVID-19 patients: A meta-analysis of cohort and randomized controlled trials.

Background: Colchicine is well known drug for the treatment of acute gout. Recently, it has also been used in the management of COVID-19 patients. Aim: The aim of current study is to find out the role of colchicine in COVID-19 patients. Material & methods: The relevant studies were searched in PubMed/Medline, Google scholar and clinical trail.gov.com till inception and sorted based on the inclusion and exclusion criteria. The quality assessment of studies were done using Newcastle Ottawa Quality Assessment Scale. The pooled estimate was calculated as odd ratio and pooled prevalence with 95% confidence interval. A random effect model was used and publication bias was assessed qualitatively by trim and fill method. Results: Out of 38 studies, a total of 6 studies were found relevant for the analysis containing 1146 patients (705 males and 441 females). The pooled odd ratio was found to be 0.35 [0.23, 0.53] which indicate significance reduction of mortality in colchicine group as compared to non-colchicine group. The pooled prevalence of the patients treated with colchicine were found to be significant [0.11(0.03, 0.24)]. The heterogeneity among studies was also found to be low (I2 = 11%). However, funnel plot has indicated the involvement of publication bias [Egger: bias = 10.168291 (95% CI = 5.042044 to 15.294537) P = 0.0053]. Conclusion: Colchicine might be helpful in reduction of mortality in the management of COVID-19 patients. However, further studies are required to confirm its exact role.

Redesigning navigational aids using virtual global landmarks to improve spatial knowledge retrieval.

Although beacon- and map-based spatial strategies are the default strategies for navigation activities, today's navigational aids mostly follow a beacon-based design where one is provided with turn-by-turn instructions. Recent research, however, shows that our reliance on these navigational aids is causing a decline in our spatial skills. We are processing less of our surrounding environment and relying too heavily on the instructions given. To reverse this decline, we need to engage more in map-based learning, which encourages the user to process and integrate spatial knowledge into a cognitive map built to benefit flexible and independent spatial navigation behaviour. In an attempt to curb our loss of skills, we proposed a navigation assistant to support map-based learning during active navigation. Called the virtual global landmark (VGL) system, this augmented reality (AR) system is based on the kinds of techniques used in traditional orienteering. Specifically, a notable landmark is always present in the user's sight, allowing the user to continuously compute where they are in relation to that specific location. The efficacy of the unit as a navigational aid was tested in an experiment with 27 students from the University of Technology Sydney via a comparison of brain dynamics and behaviour. From an analysis of behaviour and event-related spectral perturbation, we found that participants were encouraged to process more spatial information with a map-based strategy where a silhouette of the compass-like landmark was perpetually in view. As a result of this technique, they consistently navigated with greater efficiency and better accuracy.

3-aminoquinoline: a turn-on fluorescent probe for preferential solvation in binary solvent mixtures.

3-Aminoquinoline (3AQ) has been used as a fluorescent probe for preferential solvation in hexane-ethanol solvent mixtures. Results of the present experiment have been put into context by comparison with prior observations with 5-aminoquinoline (5AQ) as the probe. 3AQ exhibits a relatively small change of dipole moment (Δµ= 2.2 D) upon photoexcitation, compared to 5AQ (Δµ= 6.1D), which might appear to be a hindrance in the way of its use as a solvation probe. Indeed, the values of parameters like spectral shifts are smaller for the present experiment with 3AQ. At the smallest concentration of alcohol used, its local mole fraction around the probe is significantly lower than in the previous experiments with 5AQ. However, these apparent disadvantages are outweighed by the significant increase in fluorescence intensity and lifetime observed with increasing concentration of ethanol in the solvent mixture, as opposed to the drastic fluorescence quenching that occurs for 5AQ. This is a marked advantage in the use of 3AQ in studies like the present one. The local mole fraction of ethanol and preferential solvation index experienced by 3AQ are in line with those reported for 5AQ. The disadvantage of the smaller magnitude of Δµpersists in the time resolved fluorescence experiments, for solvent mixtures with very low ethanol content. Negligible wavelength dependence of fluorescence transients of 3AQ is observed forxp= 0.002,. However, this effect is outweighed at higher alcohol concentrations, for which nanosecond dynamics of preferential solvation is observed.

EEG Peak Detection in Cognitive Conflict Processing Using Summit Navigator and Clustering-Based Ranking.

Correct detection of peaks in electroencephalogram (EEG) signals is of essence due to the significant correlation of those potentials with cognitive performance and disorders. This paper proposes a novel and non-parametric approach to detect prediction error negativity (PEN) in cognitive conflict processing. The PEN candidates are first located from the input signal via an adaptation of a recent effective method for local maxima extraction, processed in a multi-scale manner. The found candidates are then fused and ranked based on their shape and location-based features. False positives caused by candidates' magnitude are eliminated by rotating the sorted candidate list where the one with the second-best ranking score will be identified as PEN. The EEG data collected from a 3D object selection task have been used to verify the efficacy of the proposed approach. Compared with the state-of-the-art peak detection techniques, the proposed method shows an improvement of at least 2.67% in accuracy and 6.27% in sensitivity while requires only about 4 ms to process an epoch. The accuracy and computational efficiency of the proposed technique in the detection of PEN in cognitive conflict processing would lead to promising applications in performance improvement of brain-computer interfaces (BCIs).

In-silico neuro musculoskeletal model reproduces the movement types obtained by spinal micro stimulation.

BACKGROUND AND OBJECTIVES: Virtual patients and physiologies allow experimentation, design, and early-stage clinical trials in-silico. Virtual patient technology for human movement systems that encompasses musculoskeleton and its neural control are few and far in between. Our major goal is to create a neuro- musculoskeletal upper limb in-silico model, which is modular in architecture and generates movement as an emergent phenomenon out of a multiscale co-simulation of spinal cord neural control and musculoskeletal dynamics. METHODS: The model is developed on the NEUROiD movement simulation platform that enables a co-simulation of popular neural simulator NEURON and the musculoskeletal simulator OpenSim. We further characterized and demonstrated the use of this model in generating a range of commonly observed upper limb movements by means of a spatio-temporal stimulation pattern delivered to the cervical spinal cord. RESULTS: We were able to characterize the model based on proprioception (Ia, Ib and II fibers), afferent conduction delay and inital postures of the musculoskeletal system. A smooth movement was achieved in all the considered experiments. The generated movements in all degrees of freedom were reproduced in accordance with the previous experimental studies. CONCLUSION: In this work, design and development of the upper limb model was described in a modular fashion, while reusing existing models and modules. We believe this work enables a first and small step towards an in-silico paradigms for understanding upper limb movement, disease pathology, medication, and rehabilitation.

Using virtual global landmark to improve incidental spatial learning.

To reduce the decline of spatial cognitive skills caused by the increasing use of automated GPS navigation, the virtual global landmark (VGL) system is proposed to help people naturally improve their sense of direction. Designed to accompany a heads-up navigation system, VGL system constantly displays silhouette of global landmarks in the navigator's vision as a notable frame of reference. This study exams how VGL system impacts incidental spatial learning, i.e., subconscious spatial knowledge acquisition. We asked 55 participants to explore a virtual environment and then draw a map of what they had explored while capturing electroencephalogram (EEG) signals and eye activity. The results suggest that, with the VGL system, participants paid more attention during exploration and performed significantly better at the map drawing task-a result that indicates substantially improved incidental spatial learning. This finding might kickstart a redesigning navigation aids, to teach users to learn a route rather than simply showing them the way.