Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogeny Poorly Predicts the Utility of a Challenging Horizontally Transferred Gene in Methylobacterium Strains

ABSTRACT Horizontal gene transfer plays a crucial role in microbial evolution. While much is known about the mechanisms that determine whether physical DNA can be transferred into a new host, the factors determining the utility of the transferred genes are less clear. We have explored this issue using dichloromethane consumption in Methylobacterium strains. Methylobacterium extorquens DM4 expresses a dichloromethane dehalogenase (DcmA) that has been acquired through horizontal gene transfer and allows the strain to grow on dichloromethane as the sole carbon and energy source. We transferred the dcmA gene into six Methylobacterium strains that include both close and distant evolutionary relatives. The transconjugants varied in their ability to grow on dichloromethane, but their fitness on dichloromethane did not correlate with the phylogeny of the parental strains or with any single tested physiological factor. This work highlights an important limiting factor in horizontal gene transfer, namely, the capacity of the recipient strain to accommodate the stress and metabolic disruption resulting from the acquisition of a new enzyme or pathway. Understanding these limitations may help to rationalize historical examples of horizontal transfer and aid deliberate genetic transfers in biotechnology for metabolic engineering.
Abnormal EEG Responses to TMS During the Cortical Silent Period Are Associated With Hand Function in Chronic Stroke

Background. Abnormal brain excitability influences recovery after stroke at which time a prolonged transcranial magnetic stimulation (TMS)–induced electromyographic silent period is thought to reflect abnormal inhibitory interneuron excitability. Cortical excitability can be probed directly during the silent period using concurrent electroencephalography (EEG) of TMS-evoked responses. Objective. The primary study objectives were to characterize TMS-evoked cortical potentials (TEPs) using EEG and to investigate associations with persistent hand and arm motor dysfunction in individuals with chronic stroke. Methods. Thirteen participants with chronic stroke-related mild-moderate arm motor impairment and 12 matched controls completed a single TMS-EEG cortical excitability assessment. TEPs recorded from the vertex during cortical silent period (CSP) assessment and while at rest were used to evaluate differences in cortical excitability between stroke and control participants. Associations between TEPs and CSP duration with measures of upper extremity motor behavior were investigated. Results. Significantly increased TEP component peak amplitudes and delayed latencies were observed for stroke participants compared with controls during CSP assessment and while at rest. Delayed early TEP component (P30) peak latencies during CSP assessment were associated with less manual dexterity. CSP duration was prolonged in stroke participants, and correlated with P30 peak latency and paretic arm dysfunction. Conclusions. Abnormal cortical excitability directly measured by early TMS-evoked EEG responses during CSP assessment suggests abnormal cortical inhibition is associated with hand dysfunction in chronic stroke. Further investigation of abnormal cortical inhibition in specific brain networks is necessary to characterize the salient neurophysiologic mechanisms contributing to persistent motor dysfunction after stroke.
Deciphering the Function of New Gonococcal Vaccine Antigens Using Phenotypic Microarrays

ABSTRACT The function and extracellular location of cell envelope proteins make them attractive candidates for developing vaccines against bacterial diseases, including challenging drug-resistant pathogens, such as Neisseria gonorrhoeae. A proteomics-driven reverse vaccinology approach has delivered multiple gonorrhea vaccine candidates; however, the biological functions of many of them remain to be elucidated. Herein, the functions of six gonorrhea vaccine candidates—NGO2121, NGO1985, NGO2054, NGO2111, NGO1205, and NGO1344—in cell envelope homeostasis were probed using phenotype microarrays under 1,056 conditions and a ΔbamE mutant (Δngo1780) as a reference of perturbed outer membrane integrity. Optimal growth conditions for an N. gonorrhoeae phenotype microarray assay in defined liquid medium were developed, which can be useful in other applications, including rapid and thorough antimicrobial susceptibility assessment. Our studies revealed 91 conditions having uniquely positive or negative effects on one of the examined mutants. A cluster analysis of 37 and 57 commonly beneficial and detrimental compounds, respectively, revealed three separate phenotype groups: NGO2121 and NGO1985; NGO1344 and BamE; and the trio of NGO1205, NGO2111, and NGO2054, with the last protein forming an independent branch of this cluster. Similar phenotypes were associated with loss of these vaccine candidates in the highly antibiotic-resistant WHO X strain. Based on their extensive sensitivity phenomes, NGO1985 and NGO2121 appear to be the most promising vaccine candidates. This study establishes the principle that phenotype microarrays can be successfully applied to a fastidious bacterial organism, such as N. gonorrhoeae. IMPORTANCE Innovative approaches are required to develop vaccines against prevalent and neglected sexually transmitted infections, such as gonorrhea. Herein, we have utilized phenotype microarrays in the first such investigation into Neisseria gonorrhoeae to probe the function of proteome-derived vaccine candidates in cell envelope homeostasis. Information gained from this screening can feed the vaccine candidate decision tree by providing insights into the roles these proteins play in membrane permeability, integrity, and overall N. gonorrhoeae physiology. The optimized screening protocol can be applied in investigations into the function of other hypothetical proteins of N. gonorrhoeae discovered in the expanding number of whole-genome sequences, in addition to revealing phenotypic differences between clinical and laboratory strains.
Accelerating Stroke Recovery: Body Structures and Functions, Activities, Participation, and Quality of Life Outcomes From a Large Rehabilitation Trial

Background. Task-oriented therapies have been developed to address significant upper extremity disability that persists after stroke. Yet, the extent of and approach to rehabilitation and recovery remains unsatisfactory to many. Objective. To compare a skill-directed investigational intervention with usual care treatment for body functions and structures, activities, participation, and quality of life outcomes. Methods. On average, 46 days poststroke, 361 patients were randomized to 1 of 3 outpatient therapy groups: a patient-centered Accelerated Skill Acquisition Program (ASAP), dose-equivalent usual occupational therapy (DEUCC), or usual therapy (UCC). Outcomes were taken at baseline, posttreatment, 6 months, and 1 year after randomization. Longitudinal mixed effect models compared group differences in poststroke improvement during treatment and follow-up phases. Results. Across all groups, most improvement occurred during the treatment phase, followed by change more slowly during follow-up. Compared with DEUCC and UCC, ASAP group gains were greater during treatment for Stroke Impact Scale Hand, Strength, Mobility, Physical Function, and Participation scores, self-efficacy, perceived health, reintegration, patient-centeredness, and quality of life outcomes. ASAP participants reported higher Motor Activity Log–28 Quality of Movement than UCC posttreatment and perceived greater study-related improvements in quality of life. By end of study, all groups reached similar levels with only limited group differences. Conclusions. Customized task-oriented training can be implemented to accelerate gains across a full spectrum of patient-reported outcomes. While group differences for most outcomes disappeared at 1 year, ASAP participants achieved these outcomes on average 8 months earlier (ClinicalTrials.gov: Interdisciplinary Comprehensive Arm Rehabilitation Evaluation [ICARE] Stroke Initiative, at www.ClinicalTrials.gov/ClinicalTrials.gov. Identifier: NCT00871715).
Neurofeedback Training Aimed to Improve Focused Attention and Alertness in Children With ADHD

Neurofeedback is a nonpharmacological treatment for attention-deficit hyperactivity disorder (ADHD). We propose that operant conditioning of electroencephalogram (EEG) in neurofeedback training aimed to mitigate inattention and low arousal in ADHD, will be accompanied by changes in EEG bands’ relative power. Patients were 18 children diagnosed with ADHD. The neurofeedback protocol (“Focus/Alertness” by Peak Achievement Trainer) has a focused attention and alertness training mode. The neurofeedback protocol provides one for Focus and one for Alertness. This does not allow for collecting information regarding changes in specific EEG bands (delta, theta, alpha, low and high beta, and gamma) power within the 2 to 45 Hz range. Quantitative EEG analysis was completed on each of twelve 25-minute-long sessions using a custom-made MatLab application to determine the relative power of each of the aforementioned EEG bands throughout each session, and from the first session to the last session. Additional statistical analysis determined significant changes in relative power within sessions (from minute 1 to minute 25) and between sessions (from session 1 to session 12). Analysis was of relative power of theta, alpha, low and high beta, theta/alpha, theta/beta, and theta/low beta and theta/high beta ratios. Additional secondary measures of patients’ post-neurofeedback outcomes were assessed, using an audiovisual selective attention test (IVA + Plus) and behavioral evaluation scores from the Aberrant Behavior Checklist. Analysis of data computed in the MatLab application, determined that theta/low beta and theta/alpha ratios decreased significantly from session 1 to session 12, and from minute 1 to minute 25 within sessions. The findings regarding EEG changes resulting from brain wave self-regulation training, along with behavioral evaluations, will help elucidate neural mechanisms of neurofeedback aimed to improve focused attention and alertness in ADHD.
An Indoor Wayfinding System Based on Geometric Features Aided Graph SLAM for the Visually Impaired

This paper presents a 6-degree of freedom (DOF) pose estimation (PE) method and an indoor wayfinding system based on the method for the visually impaired. The PE method involves two-graph simultaneous localization and mapping (SLAM) processes to reduce the accumulative pose error of the device. In the first step, the floor plane is extracted from the 3-D camera’s point cloud and added as a landmark node into the graph for 6-DOF SLAM to reduce roll, pitch, and <inline-formula> <tex-math notation="LaTeX">${Z}$ </tex-math></inline-formula> errors. In the second step, the wall lines are extracted and incorporated into the graph for 3-DOF SLAM to reduce <inline-formula> <tex-math notation="LaTeX">${X}$ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">${Y}$ </tex-math></inline-formula>, and yaw errors. The method reduces the 6-DOF pose error and results in more accurate pose with less computational time than the state-of-the-art planar SLAM methods. Based on the PE method, a wayfinding system is developed for navigating a visually impaired person in an indoor environment. The system uses the estimated pose and floor plan to locate the device user in a building and guides the user by announcing the points of interest and navigational commands through a speech interface. Experimental results validate the effectiveness of the PE method and demonstrate that the system may substantially ease an indoor navigation task.
Molecular Kinetics of Reviving Bacterial Spores

ABSTRACT Bacterial spores can remain dormant for years, yet they possess a remarkable potential to rapidly resume a vegetative life form. Here, we identified a distinct phase at the onset of spore outgrowth, designated the ripening period. This transition phase is exploited by the germinating spore for molecular reorganization toward elongation and subsequent cell division. We have previously shown that spores of different ages, kept under various temperatures, harbor dissimilar molecular reservoirs (E. Segev, Y. Smith, and S. Ben-Yehuda, Cell 148:139–149, 2012). Utilizing this phenomenon, we observed that the length of the ripening period can vary according to the spore molecular content. Importantly, the duration of the ripening period was found to correlate with the initial spore rRNA content and the kinetics of rRNA accumulation upon exiting dormancy. Further, the synthesis of the ribosomal protein RplA and the degradation of the spore-specific protein SspA also correlated with the duration of the ripening period. Our data suggest that the spore molecular cargo determines the extent of the ripening period, a potentially crucial phase for a germinating spore in obtaining limited resources during revival.
TprC/D (Tp0117/131), a Trimeric, Pore-Forming Rare Outer Membrane Protein of Treponema pallidum, Has a Bipartite Domain Structure

ABSTRACT Identification of Treponema pallidum rare outer membrane proteins (OMPs) has been a longstanding objective of syphilis researchers. We recently developed a consensus computational framework that employs a battery of cellular localization and topological prediction tools to generate ranked clusters of candidate rare OMPs (D. L. Cox et al., Infect. Immun. 78:5178–5194, 2010). TP0117/TP0131 (TprC/D), a member of the T. pallidum repeat (Tpr) family, was a highly ranked candidate. Circular dichroism, heat modifiability by SDS-PAGE, Triton X-114 phase partitioning, and liposome incorporation confirmed that full-length, recombinant TprC (TprCFl) forms a β-barrel capable of integrating into lipid bilayers. Moreover, TprCFl increased efflux of terbium-dipicolinic acid complex from large unilamellar vesicles and migrated as a trimer by blue-native PAGE. We found that in T. pallidum, TprC is heat modifiable, trimeric, expressed in low abundance, and, based on proteinase K accessibility and opsonophagocytosis assays, surface exposed. From these collective data, we conclude that TprC is a bona fide rare OMP as well as a functional ortholog of Escherichia coli OmpF. We also discovered that TprC has a bipartite architecture consisting of a soluble N-terminal portion (TprCN), presumably periplasmic and bound directly or indirectly to peptidoglycan, and a C-terminal β-barrel (TprCC). Syphilitic rabbits generate antibodies exclusively against TprCC, while secondary syphilis patients fail to mount a detectable antibody response against either domain. The syphilis spirochete appears to have resolved a fundamental dilemma arising from its extracellular lifestyle, namely, how to enhance OM permeability without increasing its vulnerability to the antibody-mediated defenses of its natural human host.
Information system integration and technical efficiency in urban hospitals

This study aims to explain the relationship between information system (IS) integration and hospital efficiency, measured in two years, 1997 and 1998. The study used 349 urban hospitals in the analysis. The hospitals' IS integration strategy was measured by multiple indicators of the software system applications and IS resources used in 1997. Hospital performance was measured by the levels of efficiency, using technical efficiency scores computed by Data Envelopment Analysis (DEA) for 1997 and 1998. The DEA analysis shows that, among the urban hospitals studied, the number of efficient hospitals increased during the period 1997-1998. It was found that information system integration is statistically significantly associated with the DEA technical efficiency scores in 1997 and 1998. However, system integration is negatively associated with the 1997 efficiency score and changed to a positive direction in 1998. Hospitals that deployed a highly integrated IS strategy did not show an immediate benefit. However, the IS integration strategy enhanced hospitals' technical efficiency in the next year.
Conformational Changes of an Interdomain Linker Mediate Mechanical Signal Transmission in Sensor Kinase BvgS

ABSTRACT The whooping cough agent, Bordetella pertussis, controls the expression of its large virulence regulon in a coordinated manner through the two-component system BvgAS. BvgS is a dimeric, multidomain sensor kinase. Each monomer comprises, in succession, tandem periplasmic Venus flytrap (VFT) domains, a transmembrane segment, a cytoplasmic Per-Arnt-Sim (PAS) domain, a kinase module, and additional phosphorelay domains. BvgS shifts between kinase and phosphatase modes of activity in response to chemical modulators that modify the clamshell motions of the VFT domains. We have shown previously that this regulation involves a shift between distinct states of conformation and dynamics of the two-helix coiled-coil linker preceding the enzymatic module. In this work, we determined the mechanism of signal transduction across the membrane via a first linker, which connects the VFT and PAS domains of BvgS, using extensive cysteine cross-linking analyses and other approaches. Modulator perception by the periplasmic domains appears to trigger a small, symmetrical motion of the transmembrane segments toward the periplasm, causing rearrangements of the noncanonical cytoplasmic coiled coil that follows. As a consequence, the interface of the PAS domains is modified, which affects the second linker and eventually causes the shift of enzymatic activity. The major features of this first linker are well conserved among BvgS homologs, indicating that the mechanism of signal transduction unveiled here is likely to be generally relevant for this family of sensor kinases. IMPORTANCE Bordetella pertussis produces virulence factors coordinately regulated by the two-component system BvgAS. BvgS is a sensor kinase, and BvgA is a response regulator that activates gene transcription when phosphorylated by BvgS. Sensor kinases homologous to BvgS are also found in other pathogens. Our goal is to decipher the mechanisms of BvgS signaling, since these sensor kinases may represent new targets for antibacterial agents. Signal perception by the sensor domains of BvgS triggers small motions of the helical linker region underneath. The protein domain that follows this linker undergoes a large conformational change that amplifies the initial signal, causing a shift of activity from kinase to phosphatase. Because BvgS homologs harbor similar regions, these signaling mechanisms are likely to apply generally to that family of sensor kinases.
Decrease of Delta Oscillatory Responses in Cognitively Normal Parkinson’s Disease

Parkinson’s disease (PD) is a common progressive neurodegenerative disorder. This study aims to compare sensory-evoked oscillations (SEOs) and event-related oscillations (EROs) of visual modality in cognitively normal PD patients and healthy controls. Sixteen PD and 16 age-, gender-, and education-matched healthy controls participated in the study. A simple flashlight was used for SEO and a classical visual oddball paradigm was used for target ERO. Oscillatory responses in the delta frequency range (0.5-3.5 Hz) were examined. Significantly lower delta ERO and SEO responses were found in PD patients than healthy controls. Delta ERO responses were decreased at all frontal, central and parietal locations, whereas delta SEO responses were decreased over mid and right central locations in PD. According to the notion that SEO reflects the activity of sensory networks and ERO reflects cognitive networks, these findings indicate that PD patients have impairments in both cognitive and sensory networks of visual modality. Decreased delta ERO responses indicate that the subliminal cognitive changes in PD can be detected by electrophysiological methods. These results demonstrate that brain oscillatory responses have the potential to be studied as a biomarker for visual cognitive and sensory networks in PD.
Cochaperone Interactions in Export of the Type III Needle Component PscF of Pseudomonas aeruginosa

ABSTRACT Type III secretion (T3S) systems allow the export and translocation of bacterial effectors into the host cell cytoplasm. Secretion is accomplished by an 80-nm-long needle-like structure composed, in Pseudomonas aeruginosa, of the polymerized form of a 7-kDa protein, PscF. Two proteins, PscG and PscE, stabilize PscF within the bacterial cell before its export and polymerization. In this work we screened the 1,320-Å2 interface between the two chaperones, PscE and PscG, by site-directed mutagenesis and determined hot spot regions that are important for T3S function in vivo and complex formation in vitro. Three amino acids in PscE and five amino acids in PscG, found to be relevant for complex formation, map to the central part of the interacting surface. Stability assays on selected mutants performed both in vitro on purified PscE-PscG complexes and in vivo on P. aeruginosa revealed that PscE is a cochaperone that is essential for the stability of the main chaperone, PscG. Notably, when overexpressed from a bicistronic construct, PscG and PscF compensate for the absence of PscE in cytotoxic P. aeruginosa. These results show that all of the information needed for needle protein stabilization and folding, its presentation to the T3 secreton, and its export is present within the sequence of the PscG chaperone.
Model-Based Dynamic Control Allocation in a Hybrid Neuroprosthesis

A hybrid neuroprosthesis that combines human muscle power, elicited through functional electrical stimulation (FES), with a powered orthosis may be advantageous over a sole FES or a powered exoskeleton-based rehabilitation system. The hybrid system can conceivably overcome torque reduction due to FES-induced muscle fatigue by complementarily using torque from the powered exoskeleton. The second advantage of the hybrid system is that the use of human muscle power can supplement the powered exoskeleton’s power (motor torque) requirements; thus, potentially reducing the size and weight of a walking restoration system. To realize these advantages, however, it is unknown how to concurrently optimize desired control performance and allocation of control inputs between FES and electric motor. In this paper, a model predictive control-based dynamic control allocation (DCA) is used to allocate control between FES and the electric motor that simultaneously maintain a desired knee angle. The experimental results, depicting the performance of the DCA method while the muscle fatigues, are presented for an able-bodied participant and a participant with spinal cord injury. The experimental results showed that the motor torque recruited by the hybrid system was less than that recruited by the motor-only system, the algorithm can be easily used to allocate more control input to the electric motor as the muscle fatigues, and the muscle fatigue induced by the hybrid system was found to be less than the fatigue induced by sole FES. These results validate the aforementioned advantages of the hybrid system; thus implying the hybrid technology’s potential use in walking rehabilitation.