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1. Direct intraoperative measurement of isometric contractile properties in living human muscle

   https://doi.org/10.1113/JP284092  

   Binder‐Markey, Benjamin I. ; Persad, Lomas S. ; Shin, Alexander Y. ; Litchy, William J. ; Kaufman, Kenton R. ; Lieber, Richard L. ( April 2023 , The Journal of Physiology)

   Skeletal muscle's isometric contractile properties are one of the classic structure–function relationships in all of biology allowing for extrapolation of single fibre mechanical properties to whole muscle properties based on the muscle's optimal fibre length and physiological cross‐sectional area (PCSA). However, this relationship has only been validated in small animals and then extrapolated to human muscles, which are much larger in terms of length and PCSA. The present study aimed to measure directly thein situproperties and function of the human gracilis muscle to validate this relationship. We leveraged a unique surgical technique in which a human gracilis muscle is transferred from the thigh to the arm, restoring elbow flexion after brachial plexus injury. During this surgery, we directly measured subject specific gracilis muscle force–length relationshipin situand propertiesex vivo. Each subject's optimal fibre length was calculated from their muscle's length‐tension properties. Each subject's PCSA was calculated from their muscle volume and optimal fibre length. From these experimental data, we established a human muscle fibre‐specific tension of 171 kPa. We also determined that average gracilis optimal fibre length is 12.9 cm. Using this subject‐specific fibre length, we observed an excellent fit between experimental and theorical active length‐tension curves. However, these fibre lengths were about half of the previously reported optimal fascicle lengths of 23 cm. Thus, the long gracilis muscle appears to be composed of relatively short fibres acting in parallel that may not have been appreciated based on traditional anatomical methods.image

   Skeletal muscle's isometric contractile properties represent one of the classic structure–function relationships in all of biology and allow scaling single fibre mechanical properties to whole muscle properties based on the muscle's architecture.

   This physiological relationship has only been validated in small animals but is often extrapolated to human muscles, which are orders of magnitude larger.

   We leverage a unique surgical technique in which a human gracilis muscle is transplanted from the thigh to the arm to restore elbow flexion after brachial plexus injury, aiming to directly measure muscles propertiesin situand test directly the architectural scaling predictions.

   Using these direct measurements, we establish human muscle fibre‐specific tension of ∼170 kPa.

   Furthermore, we show that the gracilis muscle actually functions as a muscle with relatively short fibres acting in parallelvs. long fibres as previously assumed based on traditional anatomical models.

    

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2. Exploring the role of the Kölliker–Fuse nucleus in breathing variability by mathematical modelling

   https://doi.org/10.1113/JP285158  

   John, S. R. ; Barnett, W. H. ; Abdala, A. P. L. ; Zoccal, D. B. ; Rubin, J. E. ; Molkov, Y. I. ( December 2023 , The Journal of Physiology)

   The Kölliker–Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT‐like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT‐like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late‐expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing.image

   The Kölliker–Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation.

   Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations.

   By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT‐like respiratory patterns and proposes potential KF local circuit organizations.

   Two models are presented that simulate both normal breathing and RTT‐like breathing patterns.

   These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.

    

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3. Offline memory replay in recurrent neuronal networks emerges from constraints on online dynamics

   https://doi.org/10.1113/JP283216  

   Milstein, Aaron D. ; Tran, Sarah ; Ng, Grace ; Soltesz, Ivan ( August 2023 , The Journal of Physiology)

   During spatial exploration, neural circuits in the hippocampus store memories of sequences of sensory events encountered in the environment. When sensory information is absent during ‘offline’ resting periods, brief neuronal population bursts can ‘replay’ sequences of activity that resemble bouts of sensory experience. These sequences can occur in either forward or reverse order, and can even include spatial trajectories that have not been experienced, but are consistent with the topology of the environment. The neural circuit mechanisms underlying this variable and flexible sequence generation are unknown. Here we demonstrate in a recurrent spiking network model of hippocampal area CA3 that experimental constraints on network dynamics such as population sparsity, stimulus selectivity, rhythmicity and spike rate adaptation, as well as associative synaptic connectivity, enable additional emergent properties, including variable offline memory replay. In an online stimulus‐driven state, we observed the emergence of neuronal sequences that swept from representations of past to future stimuli on the timescale of the theta rhythm. In an offline state driven only by noise, the network generated both forward and reverse neuronal sequences, and recapitulated the experimental observation that offline memory replay events tend to include salient locations like the site of a reward. These results demonstrate that biological constraints on the dynamics of recurrent neural circuits are sufficient to enable memories of sensory events stored in the strengths of synaptic connections to be flexibly read out during rest and sleep, which is thought to be important for memory consolidation and planning of future behaviour.image

   A recurrent spiking network model of hippocampal area CA3 was optimized to recapitulate experimentally observed network dynamics during simulated spatial exploration.

   During simulated offline rest, the network exhibited the emergent property of generating flexible forward, reverse and mixed direction memory replay events.

   Network perturbations and analysis of model diversity and degeneracy identified associative synaptic connectivity and key features of network dynamics as important for offline sequence generation.

   Network simulations demonstrate that population over‐representation of salient positions like the site of reward results in biased memory replay.

    

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4. To what extent do physiological tolerances determine elevational range limits of mammals?

   https://doi.org/10.1113/JP284586  

   Storz, Jay F. ; Scott, Graham R. ( October 2023 , The Journal of Physiology)

   A key question in biology concerns the extent to which distributional range limits of species are determined by intrinsic limits of physiological tolerance. Here, we use common‐garden data for wild rodents to assess whether species with higher elevational range limits typically have higher thermogenic capacities in comparison to closely related lowland species. Among South American leaf‐eared mice (genusPhyllotis), mean thermogenic performance is higher in species with higher elevational range limits, but there is little among‐species variation in the magnitude of plasticity in this trait. In the North American rodent genusPeromyscus, highland deer mice (Peromyscus maniculatus) have greater thermogenic maximal oxygen uptake () than lowland white‐footed mice (Peromyscus leucopus) at a level of hypoxia that matches the upper elevational range limit of the former species. In highland deer mice, the enhanced thermogenic in hypoxia is attributable to a combination of evolved and plastic changes in physiological pathways that govern the transport and utilization of O₂and metabolic substrates. Experiments withPeromyscusmice also demonstrate that exposure to hypoxia during different stages of development elicits plastic changes in cardiorespiratory traits that improve thermogenic via distinct physiological mechanisms. Evolved differences in thermogenic capacity provide clues about why some species are able to persist in higher‐elevation habitats that lie slightly beyond the tolerable limits of other species. Such differences in environmental tolerance also suggest why some species might be more vulnerable to climate change than others.image

    

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5. Interfacial engineering of lithium‐polymer batteries with in situ UV cross‐linking

   https://doi.org/10.1002/inf2.12197  

   Rojaee, Ramin ; Plunkett, Samuel ; Rasul, Md Golam ; Cheng, Meng ; Jabbari, Vahid ; Shahbazian‐Yassar, Reza ( May 2021 , InfoMat)

   Developing promising solid‐state Li batteries with capabilities of high current densities have been a major challenge partly due to large interfacial resistance across the electrode/electrolyte interfaces. This work represents an integrated network of self‐standing polymer electrolyte and active electrode materials with in situ UV cross‐linking. This method provides a uniform morphology of composite polymer electrolyte with low thickness of 20–40 μm. This modification leads to promising cycling results with 85% specific capacity retention in Li||LiFePO₄cell over 100 cycles at high current densities of 170 mA g⁻¹(~25 μA cm⁻², 1 C)_.By applying this method, the interfacial resistance decreases as high as seven folds compared to noncross‐linked interfaces. The following work introduce a facile and cost‐effective method in developing fast‐charging self‐standing polymer batteries with enhanced electrochemical properties.

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