Genetic variants, haplotype determination, and function of novel alleles of CYP2B6 in a Han Chinese population.

Amino acid variants in protein may result in deleterious effects on enzymatic activity. In this study we investigate the DNA variants on activity of CYP2B6 gene in a Chinese Han population for potential use in precision medicine. All exons in CYP2B6 gene from 1483 Chinese Han adults (Zhejiang province) were sequenced using Sanger sequencing. The effects of nonsynonymous variants on recombinant protein catalytic activity were investigated in vitro with Sf12 system. The haplotype of novel nonsynonymous variants with other single nucleotide variants in the same allele was determined using Nanopore sequencing. Of 38 alleles listed on the Pharmacogene Variation Consortium, we detected 7 previously reported alleles and 18 novel variants, of which 11 nonsynonymous variants showed lower catalytic activity (0.00-0.60) on bupropion compared to CYP2B6*1. Further, these 11 novel star-alleles (CYP2B6*39-49) were assigned by the Pharmacogene Variation Consortium, which may be valuable for pharmacogenetic research and personalized medicine.

Are extra locking bolts or fibular plating more important in extreme nailing of distal tibia fractures? A cadaveric biomechanical analysis.

OBJECTIVES: In far-distal extra-articular tibia fracture "extreme" nailing, debate surrounds the relative biomechanical performance of plating the fibula compared with extra distal interlocks. This study aimed to evaluate several constructs for extreme nailing including one interlock (one medial-lateral interlock), one interlock + plate (one medial-lateral interlock with lateral fibula compression plating), and two interlocks (one medial-lateral interlock and one anterior-posterior interlock). METHODS: Fifteen pairs of fresh cadaver legs were instrumented with a tibial nail to the physeal scar. A 1 cm segment of bone was resected from the distal tibia 3.5 cm from the joint and an oblique osteotomy was made in the distal fibula. We loaded specimens with three different distal fixation constructs (one interlock, one interlock + plate, and two interlocks) through 10,000 cycles form 100N-700 N of axial loading. Load to failure (Newtons), angulation and displacement were also measured. RESULTS: Mean load to failure was 2092 N (one interlock), 1917 N (one interlock + plate), and 2545 N (two interlocks). Linear mixed effects modeling demonstrated that two interlocks had a load to failure 578 N higher than one interlock alone (95 % CI, 74N-1082 N; P = 0.02), but demonstrated no significant difference between one interlock and one interlock + plate. No statistically significant difference in rates or timing of displacement >2 mm or angulation >10° were demonstrated. CONCLUSIONS: When nailing far-distal extra-articular tibia and fibula fractures, adding a second interlock provides more stability than adding a fibular plate. Distal fibula plating may have minimal biomechanical effect in extreme nailing.

Biomechanical Comparison of Four- versus Six-Strand Transosseous Suture Repair for Patellar Tendon Rupture.

BACKGROUND: Surgical repair is indicated for patellar tendon ruptures that result in loss of knee extensor mechanism function. However, biomechanical studies report conflicting results when comparing transosseous suture versus suture anchor repair techniques. This discrepancy may be due to inconsistencies in experimental design as these studies use various numbers of suture strands. Therefore, the main objective of this study is to compare the ultimate load of four- versus six-strand transosseous suture repair. Secondary objectives are to compare gap formation after cyclical loading and mode of failure. METHODS: Six pairs of fresh-frozen cadaveric specimen were randomly allocated to either four- or six-strand transosseous suture repair. Specimen underwent preconditioning cyclical loading and then load to failure. RESULTS: The six-strand repair had a significantly higher maximum load to failure compared with the four-strand repair (mean difference = 319.3 N [57.9%], p = 0.03). There was no significant difference in gap length after cyclical loading or at max load. There were no significant differences in mode of failure. CONCLUSION: Utilizing a six-stand transosseous patella tendon repair construct with one additional suture increases overall construct strength by over 50% compared with a four-strand construct.

The Biomechanical Effects of Intramedullary Fixation to the Level of the Physeal Scar on Distal Tibia Fracture Stability.

INTRODUCTION: The purpose of this study was to evaluate whether intramedullary nail contact with physeal scar improves construct mechanics when treating distal tibial shaft fractures. METHODS: Axially unstable extra-articular distal tibia fractures were created in 30 fresh frozen cadaveric specimens (15 pairs, mean age 79 years). Specimens underwent intramedullary nailing to the level of the physeal scar locked with one or two interlocks or short of the physeal scar locked with two interlocks (reference group). Specimens were subjected to 800N of axial load for 25,000 cycles. Primary outcomes were stiffness before and after cyclic loading. Secondary outcomes were load to failure, load at 3 mm displacement, plastic deformation, and total deformation. RESULTS: The physeal scar with one interlock cohort demonstrated 3.8% greater stiffness before cycling ( P = 0.75) and 1.7% greater stiffness after cycling ( P = 0.86) compared with the reference group. The physeal scar with two interlocks group exhibited 0.3% greater stiffness before cycling ( P = 0.98) and 8.4% greater stiffness after cycling ( P = 0.41) in relation to the reference group. No differences were identified regarding load to failure or load at 3 mm displacement. In specimens with two interlocks, those in contact with the physeal scar demonstrated significantly less plastic ( P = 0.02) and total ( P = 0.04) deformation. CONCLUSIONS: Constructs ending at the physeal scar demonstrated stiffness and load to failure similar to those without physeal scar contact. Less plastic and total deformation was noted in two-interlock constructs with physeal scar contact, suggesting a possible protective effect provided by the physeal scar. These data argue that physeal scar contact may offer a small mechanical benefit in nailing distal tibia fractures, but clinical relevance remains unknown.

Multi-joint Assessment of Proprioception Impairments Poststroke.

OBJECTIVES: To investigate shoulder, elbow and wrist proprioception impairment poststroke. DESIGN: Proprioceptive acuity in terms of the threshold detection to passive motion at the shoulder, elbow and wrist joints was evaluated using an exoskeleton robot to the individual joints slowly in either inward or outward direction. SETTING: A university research laboratory. PARTICIPANTS: Seventeen stroke survivors and 17 healthy controls (N=34). Inclusion criteria of stroke survivors were (1) a single stroke; (2) stroke duration <1 year; and (3) cognitive ability to follow simple instructions. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Threshold detection to passive motion and detection error at the shoulder, elbow and wrist. RESULTS: There was significant impairment of proprioceptive acuity in stroke survivors as compared to healthy group at all 3 joints and in both the inward (shoulder horizontal adduction, elbow and wrist flexion, P<.01) and outward (P<.01) motion. Furthermore, the distal wrist joint showed more severe impairment in proprioception than the proximal shoulder and elbow joints poststroke (P<.01) in inward motion. Stroke survivors showed significantly larger detection error in identifying the individual joint in motion (P<.01) and the movement direction (P<.01) as compared to the healthy group. There were significant correlations among the proprioception acuity across the shoulder, elbow and wrist joints and 2 movement directions poststroke. CONCLUSIONS: There were significant proprioceptive sensory impairments across the shoulder, elbow and wrist joints poststroke, especially at the distal wrist joint. Accurate evaluations of multi-joint proprioception deficit may help guide more focused rehabilitation.

Quantitative detection of the Ralstonia solanacearum species complex in soil by qPCR combined with a recombinant internal control strain.

IMPORTANCE: DNA-based detection and quantification of soil-borne pathogens, such as the Ralstonia solanacearum species complex (RSSC), plays a vital role in risk assessment, but meanwhile, precise quantification is difficult due to the poor purity and yield of the soil DNA retrieved. The internal sample process control (ISPC) strain RsPC we developed solved this problem and significantly improved the accuracy of quantification of RSSC in different soils. ISPC-based quantitative PCR detection is a method especially suitable for the quantitative detection of microbes in complex matrices (such as soil and sludge) containing various PCR inhibitors and for those not easy to lyse (like Gram-positive bacteria, fungi, and thick-wall cells like resting spores). In addition, the use of ISPC strains removes additional workload on the preparation of high-quality template DNA and facilitates the development of high-throughput quantitative detection techniques for soil microbes.

High-Throughput, Quantitative Screening of Quorum-Sensing Inhibitors Based on a Bacterial Biosensor.

Quorum sensing (QS) is a cell-cell communication mechanism by which bacteria synchronize social behaviors such as biofilm formation and virulence factor secretion by producing and sensing small molecular signals. Quorum quenching (QQ) by degrading signals or blocking signal transmissions has become a promising strategy for disrupting QS and preventing bacterial infection and biofilm formation. However, studies of high-throughput screening and identification approaches for quorum-sensing inhibitors (QSIs) are still inadequate. In this work, we developed a sensitive, high-throughput approach for screening QSIs based on the bacterial biosensor strain Agrobacterium tumefaciens N5 (pBA7P), which contains a traG gene promoter induced by QS signals fused with a promoterless ß-lactamase gene reporter. Using this approach, we identified 31 QQ bacteria from ∼2000 soil bacterial isolates, some belonging to the genera Bosea, Cupriavidus, and Flavobacterium that have not been reported previously as QQ bacteria. We also identified four QS inhibitory compounds and one QS signal analogue from ∼5000 small-molecule compounds, which profoundly affected the expression of QS-regulated genes and phenotypes of the pathogenic bacteria. This high-throughput screening system is effective and sensitive for screening of both QQ microbes and small molecules, enabling the discovery of a wide variety of biocompatible compounds.

Regulation of 2,4-diacetylphloroglucinol biosynthesis and biocontrol capacity by the BolA family protein IbaG in Pseudomonas fluorescens 2P24.

The monothiol glutaredoxin GrxD plays an essential role in the biosynthesis of the antibiotic 2,4-diacetylphloroglucinol (2,4-DAPG) and the biocontrol capacity of the soil bacterium Pseudomonas fluorescens 2P24. However, the detailed mechanism underlying GrxD-mediated activation of the production of 2,4-DAPG remains unclear. Here, we found that GrxD directly interacted with IbaG, a BolA protein family member. The mutation of ibaG significantly decreased 2,4-DAPG production. Furthermore, expressing ibaG restored the production of 2,4-DAPG in the grxD ibaG double mutant to wild-type levels in the presence of dithiothreitol, suggesting that IbaG was required for GrxD-mediated regulation of 2,4-DAPG production. Transcriptome sequencing analyses revealed that IbaG plays a global role in gene regulation by affecting the expression of numerous genes throughout the genome. We also demonstrated that IbaG is an important regulator of several cellular processes, including swarming motility, biofilm formation, siderophore production, and acid resistance. Altogether, our data suggest that IbaG has an essential role in 2,4-DAPG production, motility, and biofilm formation. We also propose a regulatory mechanism linking GrxD to 2,4-DAPG production via IbaG. IMPORTANCE The production of 2,4-diacetylphloroglucinol (2,4-DAPG) is positively influenced by the monothiol glutaredoxin GrxD in Pseudomonas fluorescens 2P24. However, the regulatory mechanism underlying GrxD-mediated regulation of 2,4-DAPG biosynthesis is mostly uncharacterized. Here, we show the function of the BolA-like protein IbaG in 2,4-DAPG biosynthesis. We also demonstrate that GrxD directly interacts with IbaG and influences the redox state of IbaG. Altogether, this work provides new insights into the role of the highly conserved IbaG protein in regulating 2,4-DAPG synthesis, biofilm formation, and other biocontrol traits of P. fluorescens.

The Efficacy of REG Proteins as a Diagnostic Biomarker for Pancreatic Cancer: a Meta-Analysis.

BACKGROUND: Regenerating gene (REG) family proteins play a pivotal role in cell proliferation, tissue regeneration, and tumor metastasis. Recent studies have concentrated on the role of REG proteins in pancreatic cancer, but the results remain controversial. In this study, a meta-analysis was performed to evaluate the precise diagnostic value of REG proteins in pancreatic cancer. METHODS: A search was conducted in PubMed, Medline, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Biomedical Literature Database (CBM), and WANFANG Data up to May 5, 2021. The QUADAS-2 tool was used to evaluate the quality of the included studies. The statistical analysis of the diagnostic tests was conducted using RevMan5 and Meta-Disc 1.4. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95% CIs) were calculated from each eligible study. RESULTS: The meta-analysis included 15 articles containing 796 patients and 584 controls. The pooled sensitivity was 0.71 (95% CI: 0.67 - 0.74), the pooled specificity was 0.73 (95% CI: 0.70 - 0.76), and the pooled DOR was 11.35 (95% CI: 5.92 - 21.77), respectively. The overall area under the receiver operating characteristic curve (AUC) was 0.84. Spearman's correlation coefficient was 0.34 (p = 0.221). For the subgroup analysis, the REG4 protein showed higher diagnostic accuracy compared with the other REG proteins. CONCLUSIONS: REG proteins have moderate diagnostic accuracy in pancreatic cancer. Further well-designed studies with larger sample sizes and clinical application are needed to validate the results of this meta-analysis.

Abnormal coordination of upper extremity during target reaching in persons post stroke.

Understanding abnormal synergy of the upper extremity (UE) in stroke survivors is critical for better identification of motor impairment. Here, we investigated to what extent stroke survivors retain the ability to coordinate multiple joints of the arm during a reaching task. Using an exoskeleton robot, 37 stroke survivors' arm joint angles (θ) and torques (τ) during hand reaching in the horizontal plane was compared to that of 13 healthy controls. Kinematic and kinetic coordination patterns were quantified as variances of the multiple-joint angles and multiple-joint torques across trials, respectively, that were partitioned into task-irrelevant variance (TIVθ and TIVτ) and task-relevant variance (TRVθ and TRVτ). TIVθ and TRVθ (or TIVτ and TRVτ) led to consistent and inconsistent hand position (or force), respectively. The index of synergy (ISθ and ISτ) was determined as [Formula: see text] and [Formula: see text] for kinematic and kinetic coordination patterns, respectively. Both kinematic ISθ and kinetic ISτ in the stroke group were significantly lower than that of the control group, indicating stroke survivors had impaired reaching abilities in utilizing the multiple joints of the UE for successful completion of a reaching task. The reduction of kinematic ISθ in the stroke group was mainly attributed to the lower TIVθ as compared to the control group, while the reduction of kinetic ISτ was mainly due to the higher [Formula: see text] as well as lower TIVτ. Our results also indicated that stroke may lead to motor deficits in formation of abnormal kinetic synergistic movement of UE, especially during outward movement. The findings in abnormal synergy patterns provides a better understanding of motor impairment, suggesting that impairment-specific treatment could be identified to help improve UE synergies, focusing on outward movements.

Citrate Synthase GltA Modulates the 2,4-Diacetylphloroglucinol Biosynthesis of Pseudomonas fluorescens 2P24 and is Essential for the Biocontrol Capacity.

Carbon metabolism is critical for microbial physiology and remarkably affects the outcome of secondary metabolite production. The production of 2,4-diacetylphloroglucinol (2,4-DAPG), a bacterial secondary metabolite with a broad spectrum of antibiotic activity, is a major mechanism used by the soil bacterium Pseudomonas fluorescens 2P24 to inhibit the growth of plant pathogens and control disease occurrence. Strain 2P24 has evolved a complex signaling cascade to regulate the production of 2,4-DAPG. However, the role of the central carbon metabolism in modulating 2,4-DAPG production has not been fully determined. In this study, we report that the gltA gene, which encodes citrate synthase, affects the expression of the 2,4-DAPG biosynthesis gene and is essential for the biocontrol capacity of strain 2P24. Our data showed that the mutation of gltA remarkably decreased the biosynthesis of 2,4-DAPG. Consistent with this result, the addition of citrate in strain 2P24 resulted in increased 2,4-DAPG production and decreased levels of RsmA and RsmE. In comparison with the wild-type strain, the gltA mutant was severely impaired in terms of biocontrol activity against the bacterial wilt disease of tomato plants caused by Ralstonia solanacearum. Moreover, the gltA mutant exhibited increased antioxidant activity, and the expression of oxidative, stress-associated genes, including ahpB, katB, and oxyR, was significantly upregulated in the gltA mutant compared to the wild-type strain. Overall, our data indicate that the citrate synthase GltA plays an important role in the production of 2,4-DAPG and oxidative stress and is required for biocontrol capacity.

Quorum quenching by a type IVA secretion system effector.

Proteobacteria primarily utilize acyl-homoserine lactones (AHLs) as quorum-sensing signals for intra-/interspecies communication to control pathogen infections. Enzymatic degradation of AHL represents the major quorum-quenching mechanism that has been developed as a promising approach to prevent bacterial infections. Here we identified a novel quorum-quenching mechanism revealed by an effector of the type IVA secretion system (T4ASS) in bacterial interspecies competition. We found that the soil antifungal bacterium Lysobacter enzymogenes OH11 (OH11) could use T4ASS to deliver the effector protein Le1288 into the cytoplasm of another soil microbiome bacterium Pseudomonas fluorescens 2P24 (2P24). Le1288 did not degrade AHL, whereas its delivery to strain 2P24 significantly impaired AHL production through binding to the AHL synthase PcoI. Therefore, we defined Le1288 as LqqE1 (Lysobacter quorum-quenching effector 1). Formation of the LqqE1-PcoI complex enabled LqqE1 to block the ability of PcoI to recognize/bind S-adenosy-L-methionine, a substrate required for AHL synthesis. This LqqE1-triggered interspecies quorum-quenching in bacteria seemed to be of key ecological significance, as it conferred strain OH11 a better competitive advantage in killing strain 2P24 via cell-to-cell contact. This novel quorum-quenching also appeared to be adopted by other T4ASS-production bacteria. Our findings suggest a novel quorum-quenching that occurred naturally in bacterial interspecies interactions within the soil microbiome by effector translocation. Finally, we presented two case studies showing the application potential of LqqE1 to block AHL signaling in the human pathogen Pseudomonas aeruginosa and the plant pathogen Ralstonia solanacearum.

Ralstonia chuxiongensis sp. nov., Ralstonia mojiangensis sp. nov., and Ralstonia soli sp. nov., isolated from tobacco fields, are three novel species in the family Burkholderiaceae.

Eight Gram-negative, aerobic, motile with paired polar flagella and rod-shaped bacteria were isolated from six tobacco fields in Yunnan, PR China. 16S rRNA gene sequence analysis revealed that all the strains belonged to the genus Ralstonia. Among them, strain 22TCCZM03-6 had an identical 16S rRNA sequence to that of R. wenshanensis 56D2T, and the other strains were closely related to R. pickettii DSM 6297T (98.34­99.86%), R. wenshanensis 56D2T (98.70­99.64%), and R. insidiosa CCUG 46789T (97.34­98.56%). Genome sequencing yielded sizes ranging from 5.17 to 5.72 Mb, with overall G + C contents of 63.3­64.1%. Pairwise genome comparisons showed that strain 22TCCZM03-6 shared average nucleotide identity (ANI) and digital DNA­DNA hybridization (dDDH) values above the species cut-off with R. wenshanensis 56D2T, suggesting that strain 22TCCZM03-6 is a special strain of the R. wenshanensis. Five strains, including 21MJYT02-10T, 21LDWP02-16, 22TCJT01-1, 22TCCZM01-4, and 22TCJT01-2, had ANI values >95% and dDDH values >70% when compared with each other. These five strains had ANI values of 73.32­94.17% and dDDH of 22.0­55.20% with the type strains of the genus Ralstonia individually, supporting these five strains as a novel species in the genus Ralstonia. In addition, strains 21YRMH01-3T and 21MJYT02-11T represent two independent species. They both had ANI and dDDH values below the thresholds for species delineation when compared with the type species of the genus Ralstonia. In strains 21YRMH01-3T and 21MJYT02-10T, the main fatty acids were summed features 3, 8, and C16:0; however, strain 21MJYT02-11T contained C16:0, cyclo-C17:0, and summed features 3 as major fatty acids. The main polar lipids, including diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine, were identified from strains 21YRMH01-3T, 21MJYT02-10T, and 21MJYT02-11T. The ubiquinones Q-7 and Q-8 were also detected in these strains, with Q-8 being the predominant quinone. Based on the above data, we propose that the eight strains represent one known species and three novel species in the genus Ralstonia, for which the names Ralstonia chuxiongensis sp. nov., Ralstonia mojiangensis sp. nov., and Ralstonia soli sp. nov. are proposed. The type strains are 21YRMH01-3T (=GDMCC 1.3534T = JCM 35818T), 21MJYT02-10T (=GDMCC 1.3531T = JCM 35816T), and 21MJYT02-11T (=GDMCC 1.3532T = JCM 35817T), respectively.

MCP extensors respond faster than flexors in individuals with severe-to-moderate stroke-caused impairment: Evidence of uncoupled neural pathways.

Damage in the corticospinal system following stroke produces imbalance between flexors and extensors in the upper extremity, eventually leading to flexion-favored postures. The substitution of alternative tracts for the damaged corticospinal tract is known to excessively activate flexors of the fingers while the fingers are voluntarily being extended. Here, we questioned whether the cortical source or/and neural pathways of the flexors and extensors of the fingers are coupled and what factor of impairment influences finger movement. In this study, a total of seven male participants with severe-to-moderate impairment by a hemiplegic stroke conducted flexion and extension at the metacarpophalangeal (MCP) joints in response to auditory tones. We measured activation and de-activation delays of the flexor and extensor of the MCP joints on the paretic side, and force generation. All participants generated greater torque in the direction of flexion (p = 0.017). Regarding co-contraction, coupled activation of the extensor is also made during flexion in the similar way to coupled activation of the flexor made during extension. As opposite to our expectation, we observed that during extension, the extensor showed marginally significantly faster activation (p = 0.66) while it showed faster de-activation (p = 0.038), in comparison to activation and de-activation of the flexor during flexion. But movement smoothness was not affected by those factors. Our results imply that the cortical source and neural pathway for the extensors of the MCP joints are not coupled with those for the flexors of the MCP joints.

Serum glycoprotein non-metastatic melanoma protein B (GPNMB) level as a potential biomarker for diabetes mellitus-related cataract: A cross-sectional study.

Background: Diabetes mellitus (DM), a metabolic disease that has attracted significant research and clinical attention over the years, can affect the eye structure and induce cataract in patients diagnosed with DM. Recent studies have indicated the relationship between glycoprotein non-metastatic melanoma protein B (GPNMB) and DM and DM-related renal dysfunction. However, the role of circulating GPNMB in DM-associated cataract is still unknown. In this study, we explored the potential of serum GPNMB as a biomarker for DM and DM-associated cataract. Methods: A total of 406 subjects were enrolled, including 60 and 346 subjects with and without DM, respectively. The presence of cataract was evaluated and serum GPNMB levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results: Serum GPNMB levels were higher in diabetic individuals and subjects with cataract than in those without DM or cataract. Subjects in the highest GPNMB tertile group were more likely to have metabolic disorder, cataract, and DM. Analysis performed in subjects with DM elucidated the correlation between serum GPNMB levels and cataract. Receiver operating characteristic (ROC) curve analysis also indicated that GPNMB could be used to diagnose DM and cataract. Multivariable logistic regression analysis illustrated that GPNMB levels were independently associated with DM and cataract. DM was also found to be an independent risk factor for cataract. Further surveys revealed the combination of serum GPNMB levels and presence of DM was associated with a more precise identification of cataract than either factor alone. Conclusions: Increased circulating GPNMB levels are associated with DM and cataract and can be used as a biomarker of DM-associated cataract.

Characterization of the influence of the dominant tract on hand closing post stroke based on the Fugl-Meyer score.

While stroke survivors with moderate or mild impairment are typically able to open their hand at will, those with severe impairment cannot. Abnormal synergies govern the arm and hand in stoke survivors with severe impairment, so hand opening, which is required to overcome the working synergy, is an extremely difficult task for them to achieve. It is universally accepted that alternative tracts including the cortico-reticulospinal tract (CRST), employed in the case that the corticospinal tract (CST) is damaged by stroke, brings about such abnormal synergies. Here we note that hand closing is enabled by alternative tracts as well as the CST, and a research question arises: Does motor characteristics while closing the hand depend on the integrity of the CST? In this study, we evaluate the abilities of 17 stroke survivors to flex and relax the metacarpophalangeal (MCP) joints and investigate whether motor characteristics can be distinguished based on CST integrity which is estimated using upper-extremity Fugl-Meyer (UEFM) scores. UEFM scores have been perceived as an indirect indicator of CST integrity. We found that participants with the UEFM score above a certain value, who are assumed to use the CST, moves the MCP joints more smoothly (P < 0.05) and activates the flexors to flex the joints faster (P < 0.05), in comparison to participants with low UEFM scores, who are assumed to preferentially use alternative tracts. The results imply that use of alternative tracts (i.e. the CRST) results in a degradation in movement smoothness and slow activation of MCP flexors. We present evidence that responses of flexors of the MCP joints following stroke depend on the degree of impairment which is hypothesized to originate from preferentially use of different neural motor pathways.

Robotic Ankle Training Improves Sensorimotor Functions in Children with Cerebral Palsy-A Pilot Study.

Children with cerebral palsy (CP) have sensorimotor impairments including weakness, spasticity, reduced motor control and sensory deficits. Proprioceptive dysfunction compounds the decreased motor control and mobility. The aims of this paper were to (1) examine proprioceptive deficit of lower extremities of children with CP; (2) study improvement in proprioception and clinical impairments through robotic ankle training (RAT). Eight children with CP participated in a 6-week RAT with pre and post ankle proprioception, clinical, biomechanical assessment compared to the assessment of eight typically developing children (TDC). The children with CP participated in passive stretching (20 min/session) and active movement training (20 to 30 min/session) using an ankle rehabilitation robot (3 sessions/week over 6 weeks, total of 18 sessions). Proprioceptive acuity measured as the plantar and dorsi-flexion motion at which the children recognized the movement was 3.60 ± 2.28° in dorsiflexion and -3.72 ± 2.38° in plantar flexion for the CP group, inferior to that of the TDC group's 0.94 ± 0.43° in dorsiflexion (p = 0.027) and -0.86 ± 0.48° in plantar flexion (p = 0.012). After training, ankle motor and sensory functions were improved in children with CP, with the dorsiflexion strength increased from 3.61 ± 3.75 Nm to 7.48 ± 2.75 Nm (p = 0.018) and plantar flexion strength increased from -11.89 ± 7.04 Nm to -17.61 ± 6.81 Nm after training (p = 0.043). The dorsiflexion AROM increased from 5.58 ± 13.18° to 15.97 ± 11.21° (p = 0.028). The proprioceptive acuity showed a trend of decline to 3.08 ± 2.07° in dorsiflexion and to -2.59 ± 1.94° in plantar flexion (p > 0.05). The RAT is a promising intervention for children with CP to improve sensorimotor functions of the lower extremities. It provided an interactive and motivating training to engage children with CP in rehabilitation to improve clinical and sensorimotor performance.

8-oxo-dGTP curbs tumor development via S phase arrest and AIF-mediated apoptosis.

Oxidative stress can attack precursor nucleotides, resulting in nucleic acid damage in cells. It remains unclear how 8-oxo-dGTP and 8-oxoGTP, oxidized forms of dGTP and GTP, respectively, could affect DNA or RNA oxidation levels and tumor development. To address this, we intravenously administered 8-oxo-dGTP and 8-oxoGTP to wild-type and MTH1-knockout mice. 8-oxoGTP administration increased frequency of tumor incidence, which is more prominent in MTH1-knockout mice. However, 8-oxo-dGTP treatment rather reduced tumor development regardless of the mouse genotype. The tumor suppressive effects of 8-oxo-dGTP were further confirmed using xenograft and C57/6J-ApcMin/Nju mouse models. Mechanistically, 8-oxo-dGTP increased the 8-oxo-dG contents in DNA and DNA strand breakage, induced cell cycle arrest in S phase and apoptosis mediated by AIF, eventually leading to reduced tumor incidence. These results suggest distinct roles of 8-oxo-dGTP and 8-oxoGTP in tumor development.

Duplicated Flagellins in Pseudomonas Divergently Contribute to Motility and Plant Immune Elicitation.

Flagellins are the main constituents of the flagellar filaments that provide bacterial motility, chemotactic ability, and host immune elicitation ability. Although the functions of flagellins have been extensively studied in bacteria with a single flagellin-encoding gene, the function of multiple flagellin-encoding genes in a single bacterial species is largely unknown. Here, the model plant-growth-promoting bacterium Pseudomonas kilonensis F113 was used to decipher the divergent functions of duplicated flagellins. We demonstrate that the two flagellins (FliC-1 and FliC-2) in 12 Pseudomonas strains, including F113, are evolutionarily distinct. Only the fliC-1 gene but not the fliC-2 gene in strain F113 is responsible for flagellar biogenesis, motility, and plant immune elicitation. The transcriptional expression of fliC-2 was significantly lower than that of fliC-1 in medium and in planta, most likely due to variations in promoter activity. In silico prediction revealed that all fliC-2 genes in the 12 Pseudomonas strains have a poorly conserved promoter motif. Compared to the Flg22-2 epitope (relative to FliC-2), Flg22-1 (relative to FliC-1) induced stronger FLAGELLIN SENSING 2 (FLS2)-mediated microbe-associated molecular pattern-triggered immunity and significantly inhibited plant root growth. A change in the 19th amino acid in Flg22-2 reduced its binding affinity to the FLS2/brassinosteroid insensitive 1-associated kinase 1 complex. Also, Flg22-2 epitopes in the other 11 Pseudomonas strains were presumed to have low binding affinity due to the same change in the 19th amino acid. These findings suggest that Pseudomonas has evolved duplicate flagellins, with only FliC-1 contributing to motility and plant immune elicitation. IMPORTANCE Flagellins have emerged as important microbial patterns. This work focuses on flagellin duplication in some plant-associated Pseudomonas. Our findings on the divergence of duplicated flagellins provide a conceptual framework for better understanding the functional determinant flagellin and its peptide in multiple-flagellin plant-growth-promoting rhizobacteria.