In vivo vastus lateralis fascicle excursion during speed skating imitation.

Mechanical power is a key performance indicator in long track speed skating. Maximal power output in athletic performance can be achieved when mechanical properties of muscles, such as the force-length relationship, are optimized. The purpose of this study was to determine the in vivo operating range of vastus lateralis (VL) fascicle lengths during speed skating imitation and compare the fascicle lengths to those that define the VL force-length relationship. Sixteen sub-elite long track speed skaters (7 females and 9 males; body mass: 72.5 [11.5] kg; age: 22.1 [2.7] years) performed maximal voluntary isometric knee extensions at nine different knee joint positions (20-120°) on the left leg to obtain the maximal vastus lateralis (VL) force-length relationship. Participants then performed a speed skating imitation exercise, the turn-cable, at three progressive perceived efforts (50%, 75%, 100%) to identify the VL fascicle excursion during a complete imitation skating stroke. Fascicle lengths and knee joint angles were examined at initial-contact, peak EMG, and take-off. Fascicles between initial contact and peak EMG covered the descending limb of both the maximal and submaximal force-length relationships while operating over the plateau region from peak EMG to take-off. We conclude that the VL works at sub-optimal length during the gliding phase of skating, but at optimal length for maximal force production during the crucial push-off phase where propulsion is provided.

Time-resolved single-cell RNAseq profiling identifies a novel Fabp5+ subpopulation of inflammatory myeloid cells with delayed cytotoxic profile in chronic spinal cord injury.

Traumatic spinal cord injuries (SCI) are a group of highly debilitating pathologies affecting thousands annually, and adversely affecting quality of life. Currently, no fully restorative therapies exist, and SCI still results in significant personal, societal and financial burdens. Inflammation plays a major role in the evolution of SCI, with myeloid cells, including bone marrow derived macrophages (BMDMs) and microglia (MG) being primary drivers of both early secondary pathogenesis and delayed wound healing events. The precise role of myeloid cell subsets is unclear as upon crossing the blood-spinal cord barrier, infiltrating bone marrow derived macrophages (BMDMs) may take on the morphology of resident microglia, and upregulate canonical microglia markers, thus making the two populations difficult to distinguish. Here, we used time-resolved scRNAseq and transgenic fate-mapping to chart the transcriptional profiles of tissue-resident and -infiltrating myeloid cells in a mouse model of thoracic contusion SCI. Our work identifies a novel subpopulation of foam cell-like inflammatory myeloid cells with increased expression of Fatty Acid Binding Protein 5 (Fabp5) and comprise both tissue-resident and -infiltrating cells. Fabp5+ inflammatory myeloid cells display a delayed cytotoxic profile that is predominant at the lesion epicentre and extends into the chronic phase of SCI.

A possible mechanism of Cry7Ab4 protein in delaying pupation of Plutella xylostella larvae.

Cry toxins produced by Bacillus thuringiensis (Bt) are well known for their insecticidal activities against Lepidopteran, Dipteran, and Coleopteran species. In our previous work, we showed that trypsin-digested full-length Cry7Ab4 protoxin did not have insecticidal activity against Plutella xylostella larvae but strongly inhibited their growth. In this paper, we expressed and purified recombinant active Cry7Ab4 toxic core from Escherichia coli for bioassay and identified its binding proteins. Interestingly, Cry7Ab4 toxic core exhibited activity to delay the pupation of P. xylostella larvae. Using protein pull-down assay, several proteins, including basic juvenile hormone-suppressible protein 1-like (BJSP-1), were identified from the midgut juice of P. xylostella larvae as putative Cry7Ab4-binding proteins. We showed that feeding P. xylostella larval Cry7Ab4 toxic core upregulated the level of BJSP-1 mRNA in the hemocytes and fat body and decreased the free juvenile hormone (JH) level in larvae. BJSP-1 interacted with Cry7Ab4 and bound to free JH in vitro. A possible mechanism of Cry7Ab4 in delaying the pupation of P. xylostella larvae was proposed.

Kinetic Modeling of the Release of Ethylene Oxide from Sterilized Plastic Containers and its Interaction with Monoclonal Antibodies.

Ethylene oxide (ETO) is commonly used to sterilize plastic containers, but the effects of residual amounts left after sterilization on protein therapeutics are still not well understood. Here we focus primarily on the factors that influence concentrations of ETO migrating from ETO-treated plastic containers into aqueous solution. A study was designed to investigate the kinetics of this process at various temperatures, and the kinetic data could be fit with a model based on a combination of Fickean diffusion and first-order chemical reaction (to account for observed hydrolysis of ETO). The diffusion and reaction rate constants thus obtained obey Arrhenius-like temperature dependence. These results indicate that for analytical methods involving extraction into water, measurements of residual ETO in a container must account for the effects of ETO hydrolysis. Further, the effects of salt concentration and pH of the fluid in the container on accumulated ETO levels were explored. Finally, interactions of ETO with anti-streptavidin (AntiSA) Immunoglobulin G1 (IgG1) and IgG2 antibodies were studied, with ETO adducts found on all methionine residues when incubated in solutions spiked with ETO at concentrations that could be reached (based on the kinetic studies) in ETO-treated plastic vials. Overall, the likelihood of observable ETO-protein modifications upon storage in ETO-sterilized containers will depend on a complex interplay of protein properties, formulation details, storage conditions, and amount of residual ETO initially in the container. LAY ABSTRACT: Ethylene oxide (ETO) is commonly used to sterilize plastic containers, but the effects of residual amounts left after sterilization on protein therapeutics are still not well understood. Here we describe experiments exploring the factors that influence concentrations of ETO migrating from ETO-treated plastic containers into aqueous solution over time. Additionally, interactions of ETO with model antibodies were studied, with ETO adducts found on all methionine residues when incubated in solutions spiked with ETO at concentrations that could potentially be reached in ETO-treated plastic vials. Overall, the likelihood of observable ETO-protein modifications upon storage in ETO-sterilized containers will depend on a complex interplay of protein properties, formulation details, storage conditions, and amount of residual ETO initially in the container.