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Biology subjects

O'Sullivan, C.

Publications and source records attributed to O'Sullivan, C..

3 recordsLinked to original sources

Overground Gait Kinematics and Muscle Activation Patterns in the Yucatan Mini Pig

A growing number of spinal cord injury, neuromodulation, and cell therapy studies on porcine models, especially the Yucatan minipigs (YMPs), have been recently reported. This is due to the large similarities between human and porcine neuroanatomy and biomechanics. To assess treatment modalities and locomotor recovery in this model, there is an obvious need for detailed characterization of normative overground gait in neurologically intact YMPs. The objective of this study was to assess gait biomechanics and the effect of overground walking speed on gait parameters, kinematics, and electromyographic (EMG) activity in the hindlimb muscles of YMPs. Nine neurologically-intact adult YMPs were trained to walk overground in a straight line. Whole-body kinematics and EMG activity of hindlimb muscles were recorded and analyzed at 6 different speed ranges (0.4-0.59, 0.6-0.79, 0.8-0.99, 1.0-1.19, 1.2-1.39, and 1.4-1.6 m/s). A MATLAB program was developed to detect strides and gait events automatically from motion-captured data. Significant decreases in stride duration, stance and swing times and an increase in stride length were observed with increasing speed. A transition in gait pattern occurred at the 1.0m/s walking speed. Significant increases in the range of motion of the knee and ankle joints were observed at higher speeds. Also, the points of minimum and maximum knee and ankle joint angles occurred earlier in the gait cycle at higher speeds. The onset of EMG activity in the biceps femoris muscle occurred significantly earlier in the gait cycle with increasing speed. A comprehensive characterization of overground walking in neurologically-intact YMPs is provided. These normative measures set the basis against which the effects of future interventions on locomotor capacity in YMPs can be compared.

neuroscience↗

Cytoplasmic Switch of ARS2 Isoforms Promotes Nonsense-Mediated mRNA Decay and Arsenic Sensitivity

The life of RNA polymerase II (RNAPII) transcripts is shaped by the dynamic formation of mutually exclusive ribonucleoprotein complexes (RNPs) that direct transcript biogenesis and turnover. A key regulator of RNA metabolism in the nucleus is the scaffold protein ARS2 (arsenic resistance protein 2), bound to the cap binding complex (CBC). We report here that alternative splicing of ARS2s intron 5, generates cytoplasmic isoforms that lack 270 amino acids from the N-terminal of the protein and are functionally distinct from nuclear ARS2. Switching of ARS2 isoforms within the CBC in the cytoplasm has dramatic functional consequences, changing ARS2 from a NMD inhibitor to a NMD promoter that enhances the binding of UPF1 to NCBP1, ERF1 and DHX34, favouring SURF complex formation, SMG7 recruitment and transcript degradation. ARS2 isoform exchange is also relevant during arsenic stress, where cytoplasmic ARS2 promotes a global response to arsenic in a CBC-independent manner. We propose that ARS2 isoform switching promotes the proper recruitment of RNP complexes during NMD and the cellular response to arsenic stress. The existence of non-redundant ARS2 isoforms is relevant for cell homeostasis, stress response, and cancer treatment.

molecular biology↗

A fast, scalable, MinHash-based k-mer tool to assess Sequence Read Archive next generation sequence submissions.

Sequence Read Archive submissions to the National Center for Biotechnology Information often lack useful metadata, which limits the utility of these submissions. We describe a scalable k-mer based tool for fast assessment of taxonomic diversity intrinsic to submissions, independent of metadata. We show that our MinHash-based k-mer tool is accurate and scalable, offering reliable criteria for efficient selection of data for further analysis by the scientific community, at once validating submissions while also augmenting sample metadata with reliable, searchable, taxonomic terms.

genomics↗