Field Validation of a Non-carcinogenic and Eco-Friendly Disinfectant in a Stand-In Footbath for Treatment of Footrot Associated With aprV2-Positive Strains of Dichelobacter nodosus in Swiss Sheep Flocks.

A national control program for virulent footrot is currently planned in Switzerland. Since commonly used disinfectants either contain heavy metals or are carcinogenic, the aim of this study was to verify the effectiveness of an eco-friendly and non-carcinogenic candidate disinfectant against aprV2-positive strains of Dichelobacter nodosus. Additionally, the effect of the selective use of long-acting oxytetracyclines was evaluated. A total of 18 farms with confirmed footrot infection, randomly allocated to two treatment groups: (1) with antibiotics (AB; n = 9) and, (2) no antibiotics (NAB; n = 9), were included. Claws were carefully trimmed and scored using a scale from 0 (clinically healthy) to 5 (complete loss of the horn capsule) and a prewash waterbath was implemented on 11 farms. Twice-weekly, repeated whole-flock stand-in footbaths with the candidate disinfectant (6%) were performed. Additionally, animals of group AB with a score ≥ 3 were administered oxytetracyclines by injection. On all farms, 10 days after last treatment, aprV2-positive strains could not be detected by risk-based sampling for real-time PCR analysis after 7-21 (median = 12) footbaths with a minimal culling rate of non-responders on nine farms. Farms without contact to other sheep remained without clinical signs of footrot for a minimum of 245 days (mean ± standard deviation: 293.6 ± 23.6). Antibiotic treatment did not reduce the number of footbaths needed. In contrast, a mean of 3.3 disinfecting footbaths could be saved by implementing a prewash waterbath. At animal level, individual and selective use of oxytetracyclines lead to a higher chance (odds ratio = 9.95; 95% CI: 3.54-27.95; p < 0.001) for a lesion score ≥ 3 to improve to a lesion score < 3 within 2 weeks compared to treatment without antibiotics. The test disinfectant is an effective and eco-friendly alternative for the planned Swiss footrot control program and selective use of oxytetracycline has a beneficial impact on the recovery of animals with lesion scores ≥ 3

Stimulation of paralysed quadriceps muscles with sequentially and spatially distributed electrodes during dynamic knee extension

Background: During functional electrical stimulation (FES) tasks with able-bodied (AB) participants, spatially distributed sequential stimulation (SDSS) has demonstrated substantial improvements in power output and fatigue properties compared to conventional single electrode stimulation (SES). The aim of this study was to compare the properties of SDSS and SES in participants with spinal cord injury (SCI) in a dynamic isokinetic knee extension task simulating knee movement during recumbent cycling. Method: Using a case-series design, m. vastus lateralis and medialis of four participants with motor and sensory complete SCI (AIS A) were stimulated for 6 min on both legs with both electrode setups. With SES, target muscles were stimulated by a pair of electrodes. In SDSS, the distal electrodes were replaced by four small electrodes giving the same overall stimulation frequency and having the same total surface area. Torque was measured during knee extension by a dynamometer at an angular velocity of 110 deg/s. Mean power of the left and right sides (PmeanL,R) was calculated from all stimulated extensions for initial, final and all extensions. Fatigue is presented as an index value with respect to initial power from 1 to 0, whereby 1 means no fatigue. Results: SDSS showed higher PmeanL,R values for all four participants for all extensions (increases of 132% in participant P1, 100% in P2, 36% in P3 and 18% in P4 compared to SES) and for the initial phase (increases of 84%, 59%, 66%, and 16%, respectively). Fatigue resistance was better with SDSS for P1, P2 and P4 but worse for P3 (0.47 vs 0.35, 0.63 vs 0.49, 0.90 vs 0.82 and 0.59 vs 0.77, respectively). Conclusion: Consistently higher PmeanL,R was observed for all four participants for initial and overall contractions using SDSS. This supports findings from previous studies with AB participants. Fatigue properties were better in three of the four participants. The lower fatigue resistance with SDSS in one participant may be explained by a very low muscle activation level in this case. Further investigation in a larger cohort is warranted

Field Validation of a Non-carcinogenic and Eco-Friendly Disinfectant in a Stand-In Footbath for Treatment of Footrot Associated With aprV2-Positive Strains of Dichelobacter nodosus in Swiss Sheep Flocks

A national control program for virulent footrot is currently planned in Switzerland. Since commonly used disinfectants either contain heavy metals or are carcinogenic, the aim of this study was to verify the effectiveness of an eco-friendly and non-carcinogenic candidate disinfectant against aprV2-positive strains of Dichelobacter nodosus. Additionally, the effect of the selective use of long-acting oxytetracyclines was evaluated. A total of 18 farms with confirmed footrot infection, randomly allocated to two treatment groups: (1) with antibiotics (AB; n = 9) and, (2) no antibiotics (NAB; n = 9), were included. Claws were carefully trimmed and scored using a scale from 0 (clinically healthy) to 5 (complete loss of the horn capsule) and a prewash waterbath was implemented on 11 farms. Twice-weekly, repeated whole-flock stand-in footbaths with the candidate disinfectant (6%) were performed. Additionally, animals of group AB with a score ≥ 3 were administered oxytetracyclines by injection. On all farms, 10 days after last treatment, aprV2-positive strains could not be detected by risk-based sampling for real-time PCR analysis after 7–21 (median = 12) footbaths with a minimal culling rate of non-responders on nine farms. Farms without contact to other sheep remained without clinical signs of footrot for a minimum of 245 days (mean ± standard deviation: 293.6 ± 23.6). Antibiotic treatment did not reduce the number of footbaths needed. In contrast, a mean of 3.3 disinfecting footbaths could be saved by implementing a prewash waterbath. At animal level, individual and selective use of oxytetracyclines lead to a higher chance (odds ratio = 9.95; 95% CI: 3.54–27.95; p &lt; 0.001) for a lesion score ≥ 3 to improve to a lesion score &lt; 3 within 2 weeks compared to treatment without antibiotics. The test disinfectant is an effective and eco-friendly alternative for the planned Swiss footrot control program and selective use of oxytetracycline has a beneficial impact on the recovery of animals with lesion scores ≥ 3

Walking Outcome After Traumatic Paraplegic Spinal Cord Injury: The Function of Which Myotomes Makes a Difference?

BACKGROUND: Accurate prediction of walking function after a traumatic spinal cord injury (SCI) is crucial for an appropriate tailoring and application of therapeutical interventions. Long-term outcome of ambulation is strongly related to residual muscle function acutely after injury and its recovery potential. The identification of the underlying determinants of ambulation, however, remains a challenging task in SCI, a neurological disorder presented with heterogeneous clinical manifestations and recovery trajectories. OBJECTIVES: Stratification of walking function and determination of its most relevant underlying muscle functions based on stratified homogeneous patient subgroups. METHODS: Data from individuals with paraplegic SCI were used to develop a prediction-based stratification model, applying unbiased recursive partitioning conditional inference tree (URP-CTREE). The primary outcome was the 6-minute walk test at 6 months after injury. Standardized neurological assessments ≤15 days after injury were chosen as predictors. Resulting subgroups were incorporated into a subsequent node-specific analysis to attribute the role of individual lower extremity myotomes for the prognosis of walking function. RESULTS: Using URP-CTREE, the study group of 361 SCI patients was divided into 8 homogeneous subgroups. The node specific analysis uncovered that proximal myotomes L2 and L3 were driving factors for the differentiation between walkers and non-walkers. Distal myotomes L4-S1 were revealed to be responsible for the prognostic distinction of indoor and outdoor walkers (with and without aids). CONCLUSION: Stratification of a heterogeneous population with paraplegic SCI into more homogeneous subgroups, combined with the identification of underlying muscle functions prospectively determining the walking outcome, enable potential benefit for application in clinical trials and practice

Statistical Use of Argonaute Expression and RISC Assembly in microRNA Target Identification

MicroRNAs (miRNAs) posttranscriptionally regulate targeted messenger RNAs (mRNAs) by inducing cleavage or otherwise repressing their translation. We address the problem of detecting m/miRNA targeting relationships in homo sapiens from microarray data by developing statistical models that are motivated by the biological mechanisms used by miRNAs. The focus of our modeling is the construction, activity, and mediation of RNA-induced silencing complexes (RISCs) competent for targeted mRNA cleavage. We demonstrate that regression models accommodating RISC abundance and controlling for other mediating factors fit the expression profiles of known target pairs substantially better than models based on m/miRNA expressions alone, and lead to verifications of computational target pair predictions that are more sensitive than those based on marginal expression levels. Because our models are fully independent of exogenous results from sequence-based computational methods, they are appropriate for use as either a primary or secondary source of information regarding m/miRNA target pair relationships, especially in conjunction with high-throughput expression studies

Microdissection of Shoot Meristem Functional Domains

The shoot apical meristem (SAM) maintains a pool of indeterminate cells within the SAM proper, while lateral organs are initiated from the SAM periphery. Laser microdissection–microarray technology was used to compare transcriptional profiles within these SAM domains to identify novel maize genes that function during leaf development. Nine hundred and sixty-two differentially expressed maize genes were detected; control genes known to be upregulated in the initiating leaf (P0/P1) or in the SAM proper verified the precision of the microdissections. Genes involved in cell division/growth, cell wall biosynthesis, chromatin remodeling, RNA binding, and translation are especially upregulated in initiating leaves, whereas genes functioning during protein fate and DNA repair are more abundant in the SAM proper. In situ hybridization analyses confirmed the expression patterns of six previously uncharacterized maize genes upregulated in the P0/P1. P0/P1-upregulated genes that were also shown to be downregulated in leaf-arrested shoots treated with an auxin transport inhibitor are especially implicated to function during early events in maize leaf initiation. Reverse genetic analyses of asceapen1 (asc1), a maize D4-cyclin gene upregulated in the P0/P1, revealed novel leaf phenotypes, less genetic redundancy, and expanded D4-CYCLIN function during maize shoot development as compared to Arabidopsis. These analyses generated a unique SAM domain-specific database that provides new insight into SAM function and a useful platform for reverse genetic analyses of shoot development in maize

A Genome-Wide Characterization of MicroRNA Genes in Maize

MicroRNAs (miRNAs) are small, non-coding RNAs that play essential roles in plant growth, development, and stress response. We conducted a genome-wide survey of maize miRNA genes, characterizing their structure, expression, and evolution. Computational approaches based on homology and secondary structure modeling identified 150 high-confidence genes within 26 miRNA families. For 25 families, expression was verified by deep-sequencing of small RNA libraries that were prepared from an assortment of maize tissues. PCR–RACE amplification of 68 miRNA transcript precursors, representing 18 families conserved across several plant species, showed that splice variation and the use of alternative transcriptional start and stop sites is common within this class of genes. Comparison of sequence variation data from diverse maize inbred lines versus teosinte accessions suggest that the mature miRNAs are under strong purifying selection while the flanking sequences evolve equivalently to other genes. Since maize is derived from an ancient tetraploid, the effect of whole-genome duplication on miRNA evolution was examined. We found that, like protein-coding genes, duplicated miRNA genes underwent extensive gene-loss, with ∼35% of ancestral sites retained as duplicate homoeologous miRNA genes. This number is higher than that observed with protein-coding genes. A search for putative miRNA targets indicated bias towards genes in regulatory and metabolic pathways. As maize is one of the principal models for plant growth and development, this study will serve as a foundation for future research into the functional roles of miRNA genes