Physiological Society

Martial arts involve cutting, jumping and landing movements known to increase injury risk. Martial artists frequently sustain injuries. Recreational martial arts have yet to implement an evidence-informed prehabilitation programme to prevent these injuries. Here, we evaluate the Martial Arts Striking Sports prehabilitation programme (MASS-12) in a recreational setting. Three traditional martial arts warm-ups and two MASS-12 warm-ups were delivered over 2 weeks as a recreational Jiu Jitsu club hall. A coach and seven athletes (five male, two female), ranging in experience from white belt to brown belt, participated. Main Outcome Measures were the Frontal plane projection angle (FPPA), a measure of dynamic knee valgus and Single leg vertical hops (SLVH), a measure of performance. Over half of recreational athletes reported previous, serious lower limb injuries. Athlete FFPA and SLVH significantly improved (−11.9° to −1.93°, 25.2 vs 27.5 cm, respectively) after the MASS-12. Athletes appreciated the increased feedback and sense of preparedness. The coach found it easy to teach and perceived improvements in performance. The MASS-12 is easy for coaches to implement; improves lower limb alignment; and is accepted by athletes. A significant improvement on current practices, the MASS-12 should be widely implemented in recreational martial arts.

<bold>Purpose:</bold> In lung transplant (LTX) recipients, Acute cellular rejection (ACR) is identified by routine monitoring with spirometry, however, impulse oscillometery (IOS) may provide a more detailed assessment, independent of patient effort. <bold>Methods:</bold> Post LTX patients attending Royal Papworth Hospital NHS FT between the 1st of December 2023 and the 1st of October 2024, performed paired IOS and spirometry measurements. Correlations were made between IOS and spirometry parameters. The differences in IOS parameters among patients who did vs did not have a 10% decline in FEV1 were compared by Mann Whitney-u test. <bold>Results:</bold> The LTX cohort consisted of 213 patients (female 38%, median age 57). IOS parameters were most strongly correlated with FEV1, of which moderate correlations were demonstrated for R5, R5-R20, X5 and AX (r= -0.53, -0.57, 0.65 and -0.59 respectively p<0.001). 93 patients had at-least one follow-up. A moderate correlation was observed between change in FEV1 and change in R5, X5, AX and R5-R20 over time (r= -0.49, 0.60, -0.68 and -0.66 respectively p<0.001). IOS parameters except for R20, were significantly lower among patients with a 10% decline in FEV1 over time (figure .1) <bold>Conclusion:</bold> IOS parameters indicative of small airways changes are correlated with FEV1 both cross-sectionally and with respect to change over time. This highlights the potential benefit of using IOS alongside standard spirometric measurements in this patient cohort. <fig><object-id>erj;66/suppl_69/OA2234/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

Non-rapid eye movement (NREM) sleep facilitates memory consolidation by transferring information from the hippocampus to the neocortex. This transfer is thought to occur primarily when hippocampal sharp-wave ripples (SWRs) and thalamocortical spindles are synchronized. However, the mechanisms underlying this synchronization remain unknown. In this study, we investigated the role of cortical layer 1 neuron-derived neurotrophic factor (NDNF)-expressing (L1 NDNF) interneurons in gating information transfer during SWR-spindle synchronization in NREM sleep. Using simultaneous cell-type specific calcium imaging with a head-mounted microscope and local field potential recordings in freely moving mice, we compared the activity of L1 NDNF and L2/3 neurons across vigilance states and during NREM-specific oscillations. Our findings reveal that L1 NDNF neurons form three distinct populations, assembling into cell networks tuned to specific sleep stages. REM active L1 NDNF and L2/3 neurons exhibit opposite activation patterns during spindles. While L2/3 cells are mostly inactive during SWR, NREM and REM active L1 NDNF cells inhibit the network upon SWR onset depending on their coupling with spindles. L1 NDNF neurons mediate slow inhibition primarily via GABAB receptors. Systemic application of a GABAB receptor antagonist resulted in decreased neuronal coupling of pyramidal cells but did not change the responses during SWRs. Overall, these findings highlight the potential role of L1 NDNF neuron-mediated inhibition in the response to synchronized sleep oscillations, with possible implications for memory consolidation.

Abstract BackgroundThe predictive value of atrial conduction abnormalities, reflected by P-wave indices (PWI), and their association with biomarkers signaling fibrosis for the development of atrial fibrillation (AF) in patients with heart failure (HF) remains underexplored. To address this gap, we investigated the associations between PWI, fibrotic biomarkers, and the risk of incident AF in a cohort of HF patients.MethodsA total of 475 patients with new-onset or worsening HF, were followed for 5 years. Fibrosis-associated biomarkers (TIMP-2, MMP-2, MMP-3, MMP-9, ST-2, GDF-15, Gal-3) were analyzed using proximity extension assay. PWI (P-wave duration, P-wave amplitude in lead I, P-wave terminal force in V1, P-wave axis and P-wave morphology in inferior leads required for definition of interatrial block (IAB)) were derived from ECGs processed with the Glasgow algorithm. Cox regression assessed associations between the biomarkers, PWI, and incident AF.ResultsAmong 475 individuals (mean age 74.6 years; 68% male), 41 developed incident AF over 5 years. Low P-wave amplitude at inclusion correlated negatively with GDF-15 (p &lt; 0.001) and MMP-2 (p = 0.037) in both leads I and II. Six biomarkers were significantly associated with incident AF in adjusted analysis: TIMP-4 (HR 2.06, p=0.007), MMP-2 (HR 2.09, p=0.046), MMP-3 (HR 1.48, p=0.007), ST-2 (HR 1.66, p=0.003), GDF-15 (HR 2.26, p=0.001), and Gal-3 (HR 2.14, p=0.048). Among the PWI, P-wave axis &lt;0° (HR: 4.74, p = 0.021) and low P-wave amplitude in lead I (HR: 2.09, p=0.036) were significantly associated with incident AF.ConclusionsIn this long-term prospective follow-up study of patients admitted for HF, biomarkers with proven associations to fibrosis were associated with incident AF. This study also showed that low P-wave amplitude may reflect abnormal LA-conduction pathway and displaced intra-atrial conduction pattern in advanced HF, as low P-wave in lead I and abnormal P-wave axis (&lt;0 degree) were associated with incident AF.

The utilization of plant proteins to formulate edible inks for 3D/4D food printing applications may help address challenges linked to food sustainability, personalized nutrition, and security. We investigate the suitability of various plant proteins for this purpose, including their molecular, functional, and nutritional attributes. Furthermore, we examine the potential of plant protein-based edible inks in 4D printing applications, where the shape or other properties of a material change over time, enabling controlled release profiles and texture modulations. We also discuss the environmental implications, regulatory considerations, and consumer acceptance of plant-based 3D/4D printed foods. Pea and soy proteins are widely used as inks for 3D/4D food printing applications due to their excellent structure-forming abilities, as well as their functional and nutritional properties. However, solely plant protein-based inks often lack essential characteristics required for optimal performance. Their properties can be enhanced by incorporating other food ingredients, such as polysaccharides and polyphenols. As this emerging field holds promise for addressing multiple global food-related challenges, it necessitates interdisciplinary collaboration and ongoing research to unlock its full potential.

Litter size in mice is an important fitness and economic feature that is controlled by several genes and influenced by non-genetic factors too. High positive selection pressure in each generation for Litter size at birth (LSB), resulted in the development of high and low prolific lines of inbred Swiss albino mice (SAM). Despite uniform management conditions, these lines showed variability in LSB across the generation. Variation in estrous-phased ovarian gene expression between high (LSB ≥ 12) and low prolific lines (LSB ≤ 3) of F4 inbred SAM, was explored using RNA-Seq.Estrous phase assessment was done using vaginal cytology. A total of 870 differentially expressed genes (DEGs) were identified; among which, 287 genes were significantly up-regulated while 583 genes were down-regulated in HLS as compared to the LLS group. DEGs were assigned to 166 Gene Ontology (GO) terms and KEGG pathways. In HLS, the significantly up-regulated DEGs were involved in ovarian cell-cell signaling, regulation of biological activity and ovarian metabolic-associated pathways. Most down-regulated DEGs were expressed in immune-related pathways, indicating that immunological dampening is associated with a high ovulation rate and higher level of progesterone concentration leading to physiological changes responsible for higher fecundity. The present study, based on bulk RNA-seq analysis reflects the aggregate gene expression of the whole ovarian tissue, and reveals 24 DEGs that could be used as candidates for litter size attributes in future polymorphism and functional studies to gain further insights into the mechanisms underlying litter size variations in animals.

Intracellular Ca2+ signalling regulates membrane permeabilities, enzyme activity, and gene transcription amongst other functions. Large transmembrane Ca2+ electrochemical gradients and low diffusibility between cell compartments potentially generate short-lived, localised, high-[Ca2+] microdomains. The highest concentration domains likely form between closely apposed membranes, as at amphibian skeletal muscle transverse tubule-sarcoplasmic reticular (T-SR, triad) junctions. Finite element computational analysis characterised the formation and steady state and kinetic properties of the Ca2+ microdomains using established empirical physiological and anatomical values. It progressively incorporated Fick diffusion and Nernst-Planck electrodiffusion gradients, K+, Cl-, and Donnan protein, and calmodulin (CaM)-mediated Ca2+ buffering. It solved for temporal-spatial patterns of free and buffered Ca2+, Gaussian charge differences, and membrane potential changes, following Ca2+ release into the T-SR junction. Computational runs using established low and high Ca2+ diffusibility (D Ca2+) limits both showed that voltages arising from intracytosolic total [Ca2+] gradients and the counterions little affected microdomain formation, although elevated D Ca2+ reduced attained [Ca2+] and facilitated its kinetics. Contrastingly, adopting known cytosolic CaM concentrations and CaM-Ca2+ affinities markedly increased steady-state free ([Ca2+]free) and total ([Ca2+]), albeit slowing microdomain formation, all to extents reduced by high D Ca2+. However, both low and high D Ca2+ yielded predictions of similar, physiologically effective, [Ca2+-CaM]. This Ca2+ trapping by the relatively immobile CaM particularly increased [Ca2+] at the junction centre. [Ca2+]free, [Ca2+-CaM], [Ca2+], and microdomain kinetics all depended on both CaM-Ca2+ affinity and D Ca2+. These changes accompanied only small Gaussian (∼6 mV) and surface charge (∼1 mV) effects on tubular transmembrane potential at either D Ca2+. These physical predictions of T-SR Ca2+ microdomain formation and properties are compatible with the microdomain roles in Ca2+ and Ca2+-CaM-mediated signalling but limited the effects on tubular transmembrane potentials. CaM emerges as a potential major regulator of both the kinetics and the extent of microdomain formation. These possible cellular Ca2+ signalling roles are discussed in relation to possible feedback modulation processes sensitive to the μM domain but not nM bulk cytosolic, [Ca2+]free, and [Ca2+-CaM], including ryanodine receptor-mediated SR Ca2+ release; Na+, K+, and Cl- channel-mediated membrane excitation and stabilisation; and Na+/Ca2+ exchange transport.

Abstract In multicellular systems, the migration pattern of individual cells critically relies on the interactions with neighboring cells. Depending on the strength of these interactions, cells either move as a collective, as observed during morphogenesis and wound healing, or migrate individually, as it is the case for immune cells and fibroblasts. Transducers of cell-cell adhesions, such as cadherins coordinate collective dynamics by linking the cytoskeleton of neighboring cells. However, whether intercellular binding alone triggers signals that originate from within the plasma membrane itself, remains unclear. To address this question, we designed photoswitchable cell-cell adhesions that selectively connect adjacent plasma membranes without linking directly to cytoskeletal elements. We find that these intercellular adhesions are sufficient to achieve collective cell migration. Here, linking adjacent cells increases membrane tension, which activates the enzyme phospholipase D2. The resulting increase in phosphatidic acid, in turn, stimulates the mammalian target of rapamycin, a known actuator of collective cell migration. Collectively, these findings introduce a membrane-based signaling axis as promotor of collective cell dynamics, which is independent of the direct coupling of cell-cell adhesions to the cytoskeleton.

Gene expression, morphology, and electrophysiological combination are essential for assessing the dynamic development of human induced pluripotent stem cell-derived atrial- and ventricular-like cardiomyocytes (iPS-AM and iPS-VM, respectively). For iPS-AM/VM differentiation, we performed the small molecule-based temporal modulation of the retinoic acid and bone morphogenetic protein signaling pathways. We investigated the gene expression and morphology using immunofluorescence, quantitative real-time polymerase chain reaction, flow cytometry, and transmission electron microscopy as well as registered electrophysiological functions using a whole-cell patch clamp on days 20, 30, and 60 post-differentiations. Pan-cardiomyocyte marker, including troponin T2 (TNNT2) and alpha-actinin-2 (ACTN2), expressions increased both in iPS-AMs and iPS-VMs. Similarly, the mRNA expression of both iPS-AM-specific markers, ie, natriuretic peptide A (NPPA), myosin light chain 7 (MYL7), and K+ channel Kir3.4 (KCNJ5), and iPS-VM-specific markers, ie, gap junction α-1 (GJA1), myosin light chain 2 (MYL2), and alpha-1-subunit of a voltage-dependent L-type calcium channel (CACNA1C), increased from 0 to 20 days, and then decreased from 30 to 60 days. Concerning morphology, cardiac troponin-T (cTnT) arrangement was progressively organized and developed from a disorderly myofibrillar distribution to an organized sarcomere pattern both in iPS-AMs and iPS-VMs. Mitochondrial numbers gradually increased and those of lipid droplets decreased during dynamic development. Regarding physiological function, the resting and action potential amplitudes remained statistically indifferent in both cell types, and the action potential duration was prolonged during the development. IPS-AMs/VMs displayed dynamic development concerning their gene expression, morphology, and electrophysiological function. The discoveries of this study could provide novel insights into heart development and encourage further research.

Hippocampal pyramidal neuronal activity has been previously studied using conventional patch clamp in isolated cells and brain slices. We here introduce the loose patch clamping study of voltage-activated currents from in situ pyramidal neurons in murine cornus ammonis 1 hippocampal coronal slices. Depolarizing pulses of 15-ms duration elicited early transient inward, followed by transient and prolonged outward currents in the readily identifiable junctional region between the stratum pyramidalis (SP) and oriens (SO) containing pyramidal cell somas and initial segments. These resembled pyramidal cell currents previously recorded using conventional patch clamp. Shortening the depolarizing pulses to >1-2ms continued to evoke transient currents; hyperpolarizing pulses to varying voltages evoked decays whose time constants could be shortened to <1ms, clarifying the speed of clamping in this experimental system. The inward and outward currents had distinct pharmacological characteristics and voltage-dependent inactivation and recovery from inactivation. Comparative recordings from the SP, known to contain pyramidal cell somas, demonstrated similar current properties. Recordings from the SO and stratum radiatum demonstrated smaller inward and outward current magnitudes and reduced transient outward currents, consistent with previous conventional patch clamp results from their different interneuron types. The loose patch clamp method is thus useful for in situ studies of neurons in hippocampal brain slices.