Miracle-dz/UniFAR-FTUs huggingface dataset:
The dimeric form of CXCL12 binds to atypical chemokine receptor 1

Biological functions of CXCL12 dimers may be modified by the atypical receptor ACKR1. An atypical pathway for chemokine action The chemokine CXCL12 functions in tissue development, vascular integrity, hematopoiesis, and immunity. Competition between its previously described receptors (the classical receptor CXCR4 and the atypical receptor ACKR3) can regulate the availability and therefore the multiple functional effects of CXCL12. Here, using biophysical analysis and immunofluorescence microscopy, Gutjahr et al. found that another atypical receptor—ACKR1—also bound to CXCL12 and, unlike CXCR4 and ACKR3, bound more strongly to the chemokine’s dimeric form. The findings reveal a previously unknown mediator of CXCL12 signaling that adds complexity and may help to explain its functional diversity. The pleiotropic chemokine CXCL12 is involved in diverse physiological and pathophysiological processes, including embryogenesis, hematopoiesis, leukocyte migration, and tumor metastasis. It is known to engage the classical receptor CXCR4 and the atypical receptor ACKR3. Differential receptor engagement can transduce distinct cellular signals and effects as well as alter the amount of free, extracellular chemokine. CXCR4 binds both monomeric and the more commonly found dimeric forms of CXCL12, whereas ACKR3 binds monomeric forms. Here, we found that CXCL12 also bound to the atypical receptor ACKR1 (previously known as Duffy antigen/receptor for chemokines or DARC). In vitro nuclear magnetic resonance spectroscopy and isothermal titration calorimetry revealed that dimeric CXCL12 bound to the extracellular N terminus of ACKR1 with low nanomolar affinity, whereas the binding affinity of monomeric CXCL12 was orders of magnitude lower. In transfected MDCK cells and primary human Duffy-positive erythrocytes, a dimeric, but not a monomeric, construct of CXCL12 efficiently bound to and internalized with ACKR1. This interaction between CXCL12 and ACKR1 provides another layer of regulation of the multiple biological functions of CXCL12. The findings also raise the possibility that ACKR1 can bind other dimeric chemokines, thus potentially further expanding the role of ACKR1 in chemokine retention and presentation.
Research on Indoor UWB Positioning Based on Expectation Maximization in NLOS Environment

Ultra‐wide band (UWB) technology is especially suitable for indoor positioning because of its strong anti‐interference ability, it can achieve centimeter‐level positioning accuracy in the line of sight (LOS) environment, but it is challenging to construct a robust and high‐precision algorithm in indoor complex and changeable environments. Therefore, it establishes an improved standard Kalman filter (SKF) based on expectation maximization (SKF‐EM), which models the prediction error covariance and measurement noise using the maximum likelihood criterion, estimates the filter parameters online through the expectation maximum theory, and updates the Kalman filter gain according to the Kalman filter based on dropped measurements method (SKF‐DMM). Experimental results show that: in case of serious occlusion, the maximum positioning error of SKF‐EM algorithm is 1.03 m, 39% lower than that of SKF and 60.2% lower than that of UWB.
Nanopore ion sources deliver single amino acid and peptide ions directly into high vacuum

We report a nanopore ion source for mass spectrometry that delivers ions directly into high vacuum from aqueous solutions. The ion source comprises a pulled quartz capillary with a sub-100 nm opening. Ions escape an electrified meniscus between the liquid and high vacuum by ion evaporation and travel along collisionless trajectories to the ion detector. We measure mass spectra of 16 different amino acid ions as well as post-translationally modified variants of glutathione in unsolvated states using the nanopore ion source. The emitted current is composed of ions rather than charged droplets, and more than 90% of the current can be recovered in a distant collector. The nanopore ion source could enable more sensitive proteomic analyses. It circumvents the sample loss mechanisms inherent to conventional electrospray ionization (ESI), where charged droplets are sprayed into a background gas that scatters ions and degrades their transmission.
Gait as a quantitative translational outcome measure in Angelman syndrome

Angelman Syndrome (AS) is a genetic neurodevelopmental disorder characterized by developmental delay, lack of speech, seizures, intellectual disability, and walking and balance disorders. Recently, motor ability became an interesting outcome measure in AS, as it is broad including ataxia, hypotonia, delayed and abnormal walking and postural movements and affects nearly every individual with AS. We predict that gait presents a strong opportunity for rigorous, reliable, and quantitative metrics with direct translation to evaluate pharmacological, dietary, and genetic therapies. Numerous motoric deficits have been identified clinically. In this study, we used an innovative, automated gait analysis as well as gold standard motor behavioral assays to further delineate components of motor, coordination, balance, and gait impairments in an AS mouse model across development. Our study demonstrated marked global motoric deficits in AS mice, corroborating many previous reports. Uniquely, this is the first report of nuanced and pertinent aberrations in quantitative spatial and temporal components of gait between AS and wildtype littermate controls, that are analogous in AS individuals. These metrics were followed longitudinally to observe the progression of maladaptive gait in AS, a clinical phenotype. This has not been reported previously and contributes a substantial novel metric for therapeutic development. Taken together, these findings demonstrate the robust translational value in the study of nuanced motor outcomes, i.e., gait, for AS, as well as similar genetic syndromes, in the endeavor of therapeutic screening. Lay Abstract Motor behaviors, like ambulation, gross and fine motor skills, coordination and balance, are easily quantifiable and readily translational between humans and preclinical rodent models for neurodevelopmental and neurodegenerative disorders, than other domains of behavior. To that end, we investigated gait across development in a mouse model for Angelman Syndrome and elucidated onset, progression, and decline of motor deficits in innovative, nuanced, and clinically relevant manner.
ZiBuPiYin Recipe Prevented and Treated Cognitive Decline in ZDF Rats With Diabetes-Associated Cognitive Decline via Microbiota–Gut–Brain Axis Dialogue

Gut microbiota is becoming one of the key determinants in human health and disease. Shifts in gut microbiota composition affect cognitive function and provide new insights for the prevention and treatment of neurological diseases. Diabetes-associated cognitive decline (DACD) is one of the central nervous system complications of type 2 diabetes mellitus (T2DM). ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of T2DM and prevention of DACD. However, the contribution of ZBPYR treatment to the interaction between the gut microbiota and metabolism for preventing and treating DACD remains to be clarified. Here, we investigate whether the gut microbiota plays a key role in ZBPYR-mediated prevention of DACD and treatment of T2DM via incorporating microbiomics and metabolomics, and investigate the links between the microbiota–gut–brain axis interaction and the efficacy of ZBPYR in ZDF rats. In the current study, we found that ZBPYR treatment produced lasting changes in gut microbiota community and metabolites and remotely affected hippocampus metabolic changes, thereby improving memory deficits and reversing β-amyloid deposition and insulin resistance in the brain of ZDF rats from T2DM to DACD. This may be related to a series of metabolic changes affected by gut microbiota, including alanine, aspartic acid, and glutamic acid metabolism; branched-chain amino acid metabolism; short-chain fatty acid metabolism; and linoleic acid/unsaturated fatty acid metabolism. In summary, this study demonstrates that prevention and treatment of DACD by ZBPYR partly depends on the gut microbiota, and the regulatory effects of bacteria-derived metabolites and microbiota–gut–brain axis are important protective mechanisms of ZBPYR.
No Moral Wiggle Room in an Experimental Corruption Game

Recent experimental evidence reveals that information is often avoided by decision makers in order to create and exploit a so-called “moral wiggle room,” which reduces the psychological and moral costs associated with selfish behavior. Despite the relevance of this phenomenon for corrupt practices from both a legal and a moral point of view, it has hitherto never been examined in a corruption context. We test for information avoidance in a framed public procurement experiment, in which a public official receives bribes from two competing firms and often faces a tradeoff between maximizing bribes and citizen welfare. In a treatment where officials have the option to remain ignorant about the implications of their actions for citizens, we find practically no evidence of information avoidance. We discuss possible reasons for the absence of willful ignorance in our experiment.
Are People Altruistic When Making Socially Responsible Investments? Evidence From a tDCS Study

Socially responsible investment (SRI) is an emerging philosophy that integrates social and environmental impacts into investment considerations, and it has gradually developed into an important form of investment. Previous studies have shown that both financial and non-financial motivations account for SRI behaviors, but it is unclear whether the non-financial motive to adopt SRI derives from investors’ altruism. This study uses neuroscientific techniques to explore the role of altruism in SRI decision-making. Given that existing evidence has supported the involvement of the right temporoparietal junction (rTPJ) in altruism and altruistic behaviors, we used transcranial direct current stimulation (tDCS) to temporarily modulate activity in the rTPJ and tested its effect on charitable donations and SRI behaviors. We found that anodal stimulation increased the subjects’ donations, while cathodal stimulation decreased them, suggesting that tDCS changed the subjects’ levels of altruism. More importantly, anodal stimulation enhanced the subjects’ willingness to make SRIs, while cathodal stimulation did not have a significant impact. These findings indicate that altruism plays an important role in SRI decision-making. Furthermore, cathodal stimulation changed the subjects’ perceived effectiveness of charitable donation but not that of socially responsible fund. This result may help explain the inconsistent effects of cathodal stimulation on charitable donations and SRI behaviors. The main contribution of our study lies in its pioneering application of tDCS to conduct research on SRI behaviors and provision of neuroscientific evidence regarding the role of altruism in SRI decision-making.
How Do the Players Play? A Post-Genomic Analysis Paradigm to Understand Aquatic Ecosystem Processes

Culture-independent and meta-omics sequencing methods have shed considerable light on the so-called “microbial dark matter” of Earth’s environmental microbiome, improving our understanding of phylogeny, the tree of life, and the vast functional diversity of microorganisms. This influx of sequence data has led to refined and reimagined hypotheses about the role and importance of microbial biomass, that paradoxically, sequencing approaches alone are unable to effectively test. Post-genomic approaches such as metabolomics are providing more sensitive and insightful data to unravel the fundamental operations and intricacies of microbial communities within aquatic systems. We assert that the implementation of integrated post-genomic approaches, specifically metabolomics and metatranscriptomics, is the new frontier of environmental microbiology and ecology, expanding conventional assessments toward a holistic systems biology understanding. Progressing beyond siloed phylogenetic assessments and cataloging of metabolites, toward integrated analysis of expression (metatranscriptomics) and activity (metabolomics) is the most effective approach to provide true insight into microbial contributions toward local and global ecosystem functions. This data in turn creates opportunity for improved regulatory guidelines, biomarker discovery and better integration of modeling frameworks. To that end, critical aquatic environmental issues related to climate change, such as ocean warming and acidification, contamination mitigation, and macro-organism health have reasonable opportunity of being addressed through such an integrative approach. Lastly, we argue that the “post-genomics” paradigm is well served to proactively address the systemic technical issues experienced throughout the genomics revolution and focus on collaborative assessment of field-wide experimental standards of sampling, bioinformatics and statistical treatments.
Frailty Index in the Colonias on the US-Mexico Border: A Special Report

Frailty is the age-related decline in well-being. The Frailty index (FI) measures the accumulation of health deficits and reflects biopsychosocial and cultural determinants of well-being. Frailty is measured as a static phenotype or as a Frailty Index comprising a ratio of suffered health deficits and total deficits. We report a Frailty Index calculated from routinely measured clinical variables gathered from residents of two Colonias (neighborhoods) in South Texas. A Colonia is a predominantly Hispanic, economically distressed, unincorporated neighborhood. We analyzed retrospective data from 894 patients that live in two Colonias located on the Texas-Mexico border. We calculated the FI with seven physiological variables, PHQ-9 score, and the 11 domain-specific Duke Profile scores, for a total of 19 possible health deficits. FI against age separately in males (n = 272) and females (n = 622) was regressed. Females had a significantly higher starting frailty, and males had a significantly greater change rate with age. FI against age for Cameron Park Colonia and Indian Hills Colonia was regressed. We calculated a significantly higher starting FI in Indian Hills and a significantly greater change rate in Cameron Park residents. Frailty's contributors are complex, especially in neighborhoods of poverty, immigration, low education level, and high prevalence of chronic disease. We report baseline Frailty Index data from two Colonias in South Texas and the clinical and research implications.
Modelling and Control of a 2-DOF Robot Arm with Elastic Joints for Safe Human-Robot Interaction

Collaborative robots (or cobots) are robots that can safely work together or interact with humans in a common space. They gradually become noticeable nowadays. Compliant actuators are very relevant for the design of cobots. This type of actuation scheme mitigates the damage caused by unexpected collision. Therefore, elastic joints are considered to outperform rigid joints when operating in a dynamic environment. However, most of the available elastic robots are relatively costly or difficult to construct. To give researchers a solution that is inexpensive, easily customisable, and fast to fabricate, a newly-designed low-cost, and open-source design of an elastic joint is presented in this work. Based on the newly design elastic joint, a highly-compliant multi-purpose 2-DOF robot arm for safe human-robot interaction is also introduced. The mechanical design of the robot and a position control algorithm are presented. The mechanical prototype is 3D-printed. The control algorithm is a two loops control scheme. In particular, the inner control loop is designed as a model reference adaptive controller (MRAC) to deal with uncertainties in the system parameters, while the outer control loop utilises a fuzzy proportional-integral controller to reduce the effect of external disturbances on the load. The control algorithm is first validated in simulation. Then the effectiveness of the controller is also proven by experiments on the mechanical prototype.
Isolation, Identification, and Characterization of Polystyrene-Degrading Bacteria From the Gut of Galleria Mellonella (Lepidoptera: Pyralidae) Larvae

Polystyrene (PS) is a widely used petroleum-based plastic, that pollutes the environment because it is difficult to degrade. In this study, a PS degrading bacterium identified as Massilia sp. FS1903 was successfully isolated from the gut of Galleria mellonella (Lepidoptera: Pyralidae) larvae that were fed with PS foam. Scanning electron microscopy and X-ray energy dispersive spectrometry showed that the structure and morphology of the PS film was destroyed by FS 1903, and that more oxygen appeared on the degraded PS film. A water contact angle assay verified the chemical change of the PS film from initially hydrophobic to hydrophilic after degradation. X-ray photoelectron spectroscopy further demonstrated that more oxygen-containing functional groups were generated during PS degradation. After 30 days of bacterial stain incubation with 0.15 g PS, 80 ml MSM, 30°C and PS of Mn 64400 and Mw 144400 Da, the weight of the PS film significantly decreased, with 12.97 ± 1.05% weight loss. This amount of degradation exceeds or is comparable to that previously reported for other species of bacteria reported to degrade PS. These results show that Massilia sp. FS1903 can potentially be used to degrade PS waste.
Glutamate 73 Promotes Anti-arrhythmic Effects of Voltage-Dependent Anion Channel Through Regulation of Mitochondrial Ca2+ Uptake

Mitochondria critically regulate a range of cellular processes including bioenergetics, cellular metabolism, apoptosis, and cellular Ca2+ signaling. The voltage-dependent anion channel (VDAC) functions as a passageway for the exchange of ions, including Ca2+, across the outer mitochondrial membrane. In cardiomyocytes, genetic or pharmacological activation of isoform 2 of VDAC (VDAC2) effectively potentiates mitochondrial Ca2+ uptake and suppresses Ca2+ overload-induced arrhythmogenic events. However, molecular mechanisms by which VDAC2 controls mitochondrial Ca2+ transport and thereby influences cardiac rhythmicity remain elusive. Vertebrates express three highly homologous VDAC isoforms. Here, we used the zebrafish tremblor/ncx1h mutant to dissect the isoform-specific roles of VDAC proteins in Ca2+ handling. We found that overexpression of VDAC1 or VDAC2, but not VDAC3, suppresses the fibrillation-like phenotype in zebrafish tremblor/ncx1h mutants. A chimeric approach showed that moieties in the N-terminal half of VDAC are responsible for their divergent functions in cardiac biology. Phylogenetic analysis further revealed that a glutamate at position 73, which was previously described to be an important regulator of VDAC function, is sevolutionarily conserved in VDAC1 and VDAC2, whereas a glutamine occupies position 73 (Q73) of VDAC3. To investigate whether E73/Q73 determines VDAC isoform-specific anti-arrhythmic effect, we mutated E73 to Q in VDAC2 (VDAC2E73Q) and Q73 to E in VDAC3 (VDAC3Q73E). Interestingly, VDAC2E73Q failed to restore rhythmic cardiac contractions in ncx1 deficient hearts, while the Q73E conversion induced a gain of function in VDAC3. In HL-1 cardiomyocytes, VDAC2 knockdown diminished the transfer of Ca2+ from the SR into mitochondria and overexpression of VDAC2 or VDAC3Q73E restored SR-mitochondrial Ca2+ transfer in VDAC2 deficient HL-1 cells, whereas this rescue effect was absent for VDAC3 and drastically compromised for VDAC2E73Q. Collectively, our findings demonstrate a critical role for the evolutionary conserved E73 in determining the anti-arrhythmic effect of VDAC isoforms through modulating Ca2+ cross-talk between the SR and mitochondria in cardiomyocytes.
Effect of Two Unique Nanoparticle Formulations on the Efficacy of a Broadly Protective Vaccine Against Pseudomonas Aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of infections in humans. In addition to its innate antibiotic resistance, P. aeruginosa is very effective in acquiring resistance resulting in the emergence of multi-drug resistance strains and a licensed vaccine is not yet available. We have previously demonstrated the protective efficacy of a novel antigen PaF (Pa Fusion), a fusion of the type III secretion system (T3SS) needle tip protein, PcrV, and the first of two translocator proteins, PopB. PaF was modified to provide a self-adjuvanting activity by fusing the A1 subunit of the heat-labile enterotoxin from Enterotoxigenic E. coli to its N-terminus to give L-PaF. In addition to providing protection against 04 and 06 serotypes of P. aeruginosa, L-PaF elicited opsonophagocytic killing and stimulated IL-17A secretion, which have been predicted to be required for a successful vaccine. While monomeric recombinant subunit vaccines can be protective in mice, this protection often does not transfer to humans where multimeric formulations perform better. Here, we use two unique formulations, an oil-in-water (o/w) emulsion and a chitosan particle, as well as the addition of a unique TLR4 agonist, BECC438 (a detoxified lipid A analogue designated Bacterial Enzymatic Combinatorial Chemistry 438), as an initial step in optimizing L-PaF for use in humans. The o/w emulsion together with BECC438 provided the best protective efficacy, which correlated with high levels of opsonophagocytic killing and IL-17A secretion, thereby reducing the lung burden among all the vaccinated groups tested.
The Effect of Fatigue on Single-Leg Postural Sway and Its Transient Characteristics in Healthy Young Adults

Neuromuscular fatigue is known to impair balance ability, which is reflected in increased postural sway during quiet standing tasks. Recently, quantifying transient characteristics of postural sway has been suggested as an approach to obtain additional information regarding postural control. However, this approach is currently vastly unexplored. The purpose of this study was to investigate the effects of fatigue (induced by a repeated change of direction task) on postural sway and its transient characteristics during single-leg standing, including whole-trial estimates and indexes of transient behavior in young healthy active adults. The study involved 28 physically active students (14 females). Single-leg postural sway was recorded for 30s before and after a fatiguing protocol, which consisted of a repeated change of direction tasks. We calculated the traditional whole-trial estimates of postural sway [center-of-pressure (CoP) velocity and amplitude in anterior-posterior (AP) and medial-lateral (ML) directions] and corresponding transient behavior indexes, based on three 10-s intervals. Statistically significant sex×fatigue interaction with medium effect sizes was found for whole-trial CoP velocity in AP (p=0.028; η2=0.17) and ML directions (p=0.019; η2=0.19). Post-hoc test showed that both variables substantially decreased in female participants (p=0.041–0.045; d=0.54–0.56), but remained similar in males (p=0.194–0.294). There were small to medium statistically significant main effects of fatigue on transient index for CoP amplitude in both directions (p=0.042–0.049; η2=0.02–0.14). Notably, CoP AP amplitude increased in the first 10-s interval for males (before fatigue: 5.6±1.3mm; after fatigue: 6.3±1.6mm), while the CoP AP amplitude in the third interval remained similar after fatigue (before fatigue: 5.5±1.4mm; after fatigue: 5.1±1.2mm). In conclusion, the responses to fatigue in terms of postural sway were time interval specific, and there were certain sex-differences in responses to fatigue, which could be related to better ability to adapt balance strategies in females. Moreover, our results demonstrate that the indexes of transient behavior could perhaps detect smaller fatigue-induced changes in postural sway that are seen in whole-trial estimates.