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The detailed evaluation of environmental parameters can be a great tool for the optimal selection and location of vegetable species, not only in vegetable production facilities and greenhouses but also in zoological and botanical gardens, which frequently maintain delicate and exotic plant species with strict environmental requirements in immersive exhibits where conditions can vary remarkably. This study, developed at an indoor zoological garden (Biodomo—Parque de las Ciencias de Granada, Spain), evaluates a sampling protocol for the determination of seven environmental parameters: daily light integral (DLI) was determined at nine different locations of the facility using a portable Light Quantum SQ-500 sensor; air temperature, atmospheric pressure, and air relative humidity were measured using a fixed ATMOS14 sensor; and soil temperature, soil water content, and soil conductivity were determined using a fixed TEROS12 sensor. Values recorded for DLI showed statistically significant variations across the nine different sampling locations, as well as between the different months in all sampling spots. Significant variations were also detected across the 12 months of study for the rest of environmental parameters evaluated, and correlations were found between the studied parameters, with the correlation between soil and air temperature the strongest (rs = 0.758) and soil temperature significantly superior to air temperature. The methodology described in this study can be easily reproduced in similar indoor zoological and botanical facilities, increasing the knowledge of the environmental conditions, and allowing corrections that could improve species selection, location, and management.

Background Knowledge of the muscle’s lengths at which maximum active isometric force is attained is important for predicting forces during movement. However, there is limited information about the in vivo force-length properties of a human muscle that plays crucial roles during locomotion; the tibialis anterior (TA). We therefore aimed to estimate TA’s force-length relation from dorsiflexor torque-angle curves constructed from eight women and eight men. Methods Participants performed maximal voluntary fixed-end contractions with their right ankle dorsiflexors from 0° to 30° plantar flexion. Muscle fascicle lengths were estimated from B-mode ultrasound images, and net ankle joint torques were measured using dynamometry. Fascicle forces were estimated by dividing maximal active torques by literature-derived, angle-specific tendon moment arm lengths while assuming a fixed 50% force contribution of TA to the total dorsiflexor force and accounting for fascicle angles. Results Maximal active torques were higher at 15° than 20° and 30° plantar flexion (2.4–6.4 Nm, p ≤ 0.012), whereas maximal active TA fascicle forces were higher at 15° than 0°, 20° and 30° plantar flexion (25–61 N, p ≤ 0.042), but not different between 15° and 10° plantar flexion (15 N, p = 0.277). TA fascicle shortening magnitudes during fixed-end contractions were larger at 15° than 30° plantar flexion (3.9 mm, p = 0.012), but less at 15° than 0° plantar flexion (−2.4 mm, p = 0.001), with no significant differences (≤0.7 mm, p = 0.871) between TA’s superficial and deep muscle compartments. Series elastic element stiffness was lowest and highest at lengths 5% shorter and 5% longer than optimum fascicle length, respectively (−30 and 15 N/mm, p ≤ 0.003). Discussion TA produced its maximum active force at 10–15° plantar flexion, and its normalized force-length relation had ascending and descending limbs that agreed with a simple scaled sarcomere model when active fascicle lengths from within TA’s superficial or deep muscle compartment were considered. These findings can be used to inform the properties of the contractile and series elastic elements of Hill-type muscle models.

Abstract Objective Doppler echocardiographic aortic valve peak velocity and peak pressure gradient assessment across the aortic valve (AV) is the mainstay for diagnosing aortic stenosis. Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) is emerging as a valuable diagnostic tool for estimating the peak pressure drop across the aortic valve, but assessment remains cumbersome. We aimed to validate a novel semi-automated pipeline 4D flow CMR method of assessing peak aortic value pressure gradient (AVPG) using the commercially available software solution, CAAS MR Solutions, against invasive angiographic methods. Results We enrolled 11 patients with severe AS on echocardiography from the EurValve programme. All patients had pre-intervention doppler echocardiography, invasive cardiac catheterisation with peak pressure drop assessment across the AV and 4D flow CMR. The peak AVPG was 51.9 ± 35.2 mmHg using the invasive pressure drop method and 52.2 ± 29.2 mmHg for the 4D flow CMR method (semi-automated pipeline), with good correlation between the two methods (r = 0.70, p = 0.017). Assessment of AVPG by 4D flow CMR using the novel semi-automated pipeline method shows excellent agreement to invasive assessment when compared to doppler-based methods and advocate for its use as complementary to echocardiography.

Summary: Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and association with autoimmune disease. To better understand the structural basis of IL-21 signaling, we determine the structure of the IL-21–IL-21R–γc ternary signaling complex by X-ray crystallography and a structure of a dimer of trimeric complexes using cryo-electron microscopy. Guided by the structure, we design analogs of IL-21 by introducing substitutions to the IL-21–γc interface. These IL-21 analogs act as partial agonists that modulate downstream activation of pS6, pSTAT3, and pSTAT1. These analogs exhibit differential activity on T and B cell subsets and modulate antibody production in human tonsil organoids. These results clarify the structural basis of IL-21 signaling and offer a potential strategy for tunable manipulation of humoral immunity.

Summary: The vertebrate inner retina is driven by photoreceptors whose outputs are already pre-processed; in zebrafish, outer retinal circuits split “color” from “grayscale” information across four cone-photoreceptor types. It remains unclear how the inner retina processes incoming spectral information while also combining cone signals to shape grayscale functions. We address this question by imaging the light-driven responses of amacrine cells (ACs) and bipolar cells (BCs) in larval zebrafish in the presence and pharmacological absence of inner retinal inhibition. We find that ACs enhance opponency in some bipolar cells while at the same time suppressing pre-existing opponency in others, so that, depending on the retinal region, the net change in the number of color-opponent units is essentially zero. To achieve this “dynamic balance,” ACs counteract intrinsic color opponency of BCs via the On channel. Consistent with these observations, Off-stratifying ACs are exclusively achromatic, while all color-opponent ACs stratify in the On sublamina.

Abstract Metal nanoclusters (NCs) are ultrasmall molecular aggregates consisting of dozens to hundreds of metal atoms consolidated by organic ligands, which represent an emerging area of nanoscience. Amide a myriad of metal NCs, copper NCs (CuNCs) comprise a low‐cost, high‐value subclass that has attracted great attention. The variable copper cores and diversity of protecting ligands have rendered CuNCs interesting molecular aggregates featuring structural and compositional versatility, hence showing distinctive properties and potential applications. In the present review, we have summarized the progress on atomically precise CuNCs that exhibit a range of appealing properties and applications in different fields. This review is expected to provide not only an overview of the current development on atomically precise CuNCs, but also possible directions for the future design of novel CuNCs for fundamental studies and practical applications.

The optomotor response (OMR) is central to the locomotory behavior in diverse animal species including insects, fish and mammals. Furthermore, the study of the OMR in larval zebrafish has become a key model system for investigating the neural basis of sensorimotor control. However, a comprehensive understanding of the underlying control algorithms is still outstanding. In fish it is often assumed that the OMR, by reducing average optic flow across the retina, serves to stabilize position with respect to the ground. Yet the degree to which this is achieved, and how it could emerge from the intermittent burst dynamics of larval zebrafish swimming, are unclear. Here, we combine detailed computational modeling with a new approach to free-swimming experiments in which we control the amount of visual feedback produced by a given motor effort by varying the height of the larva above a moving grid stimulus. We develop an account of underlying feedback control mechanisms that describes both the bout initiation process and the control of swim speed during bouts. We observe that the degree to which fish stabilize their position is only partial and height-dependent, raising questions about its function. We find the relative speed profile during bouts follows a fixed temporal pattern independent of absolute bout speed, suggesting that bout speed and bout termination are not separately controlled. We also find that the reverse optic flow, experienced when the fish is swimming faster than the stimulus, plays a minimal role in control of the OMR despite carrying most of the sensory information about self-movement. These results shed new light on the underlying dynamics of the OMR in larval zebrafish and will be crucial for future work aimed at identifying the neural basis of this behavior.

Regenerative medicine aims to repair degenerate tissue through cell refurbishment with minimally invasive procedures. Adipose tissue (FAT)-derived stem or stromal cells are a convenient autologous choice for many regenerative cell therapy approaches. The intervertebral disc (IVD) is a suitable target. Comprised of an inner nucleus pulposus (NP) and an outer annulus fibrosus (AF), the degeneration of the IVD through trauma or aging presents a substantial socio-economic burden worldwide. The avascular nature of the mature NP forces cells to reside in a unique environment with increased lactate levels, conditions that pose a challenge to cell-based therapies. We assessed adipose and IVD tissue-derived stromal cells through in vitro transcriptome analysis in 2D and 3D culture and suggested that the transcription factor Glis1 and metabolite oxaloacetic acid (OAA) could provide NP cells with survival tools for the harsh niche conditions in the IVD.

The overwhelming increase in the prevalence of obesity and related disorders in recent years is one of the greatest threats to the global healthcare system since it generates immense healthcare costs. As the prevalence of obesity approaches epidemic proportions, the importance of elucidating the mechanisms regulating appetite, satiety, body metabolism, energy balance and adiposity has garnered significant attention. Currently, gastrointestinal (GI) bariatric surgery remains the only approach capable of achieving successful weight loss. Appetite, satiety, feeding behavior, energy intake and expenditure are regulated by central and peripheral neurohormonal mechanisms that have not been fully elucidated yet. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Vasoactive Intestinal Polypeptide (VIP) are members of a family of regulatory peptides that are widely distributed in parallel with their specific receptors, VPAC1R, VPAC2R and PAC1R, in the central nervous system (CNS) and in the periphery, such as in the gastrointestinal tract and its associated organs and immune cells. PACAP and VIP have been reported to play an important role in the regulation of body phenotype, metabolism and homeostatic functions. The purpose of this review is to present recent data on the effects of PACAP, VIP, VPAC1R, VPAC2R and PAC1R on the modulation of appetite, satiety, metabolism, calorie intake and fat accumulation, to evaluate their potential use as therapeutic targets for the treatment of obesity and metabolic syndrome.

Abstract Background The necrotrophic fungal pathogen Pyrenophora tritici-repentis (Ptr) causes tan (syn. yellow) spot of wheat and accounts for significant yield losses worldwide. Understanding the molecular mechanisms of this economically important crop disease is crucial to counteract the yield and quality losses of wheat globally. Substantial progress has been made to comprehend the race structure of this phytopathogen based on its production of necrotrophic effectors and genomic resources of Ptr. However, one limitation for studying Ptr in a laboratory environment is the difficulty to isolate high spore numbers from vegetative growth with mycelial contamination common. These limitations reduce the experimental tractability of Ptr. Results Here, we optimized a multitude of parameters and report a sporulation method for Ptr that yields robust, high quality and pure spores. Our methodology encompasses simple and reproducible plugging and harvesting techniques, resulting in spore yields up to 1500 fold more than the current sporulation methods and was tested on multiple isolates and races of Ptr as well as an additional seven modern Australian Ptr isolates. Moreover, this method also increased purity and spore harvest numbers for two closely related fungal pathogens (Pyrenophora teres f. maculata and f. teres) that cause net blotch diseases in barley (Hordeum vulgare), highlighting the usability of this optimized sporulation protocol for the wider research community. Conclusions Large-scale spore infection and virulence assays are essential for the screening of wheat and barley cultivars and combined with the genetic mapping of these populations allows pinpointing and exploiting sources of host genetic resistance. We anticipate that improvements in spore numbers and purity will further advance research to increase our understanding of the pathogenicity mechanisms of these important fungal pathogens.

As the COVID-19 pandemic has developed, concern for invasive fungal infections in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) has emerged. We describe a clinical case of coronavirus disease (COVID-19) associated pulmonary aspergillus (CAPA) infection and acute respiratory distress syndrome (ARDS) with a good clinical outcome, in a previously well, non-immunocompromised Australian woman.

We systematically evaluate the training methodology and efficacy of two inpainting-based pretext tasks of context prediction and context restoration for medical image segmentation using self-supervised learning (SSL). Multiple versions of self-supervised U-Net models were trained to segment MRI and CT datasets, each using a different combination of design choices and pretext tasks to determine the effect of these design choices on segmentation performance. The optimal design choices were used to train SSL models that were then compared with baseline supervised models for computing clinically-relevant metrics in label-limited scenarios. We observed that SSL pretraining with context restoration using 32 × 32 patches and Poission-disc sampling, transferring only the pretrained encoder weights, and fine-tuning immediately with an initial learning rate of 1 × 10−3 provided the most benefit over supervised learning for MRI and CT tissue segmentation accuracy (p < 0.001). For both datasets and most label-limited scenarios, scaling the size of unlabeled pretraining data resulted in improved segmentation performance. SSL models pretrained with this amount of data outperformed baseline supervised models in the computation of clinically-relevant metrics, especially when the performance of supervised learning was low. Our results demonstrate that SSL pretraining using inpainting-based pretext tasks can help increase the robustness of models in label-limited scenarios and reduce worst-case errors that occur with supervised learning.

Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infection in vitro. Here we explored whether CD300lf is the sole physiologic receptor in vivo and whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strains in vitro. We further demonstrate that CD300lf is essential for both oral and parenteral MNoV infection and to elicit anti-MNoV humoral responses in vivo. In mice deficient in STAT1 signaling, CD300lf is required for MNoV-induced lethality. Finally, we demonstrate that human CD300lf (huCD300lf) is not essential for HNoV infection, nor does huCD300lf inhibit binding of HNoV virus-like particles to glycans. Thus, we report huCD300lf is not a receptor for HNoV.

Extracorporeal shock wave therapy (ESWT) is a safe and effective treatment option for various pathologies of the musculoskeletal system. Many studies address the molecular and cellular mechanisms of action of ESWT. However, to date, no uniform concept could be established on this matter. In the present study, we perform a systematic review of the effects of exposure of musculoskeletal tissue to extracorporeal shock waves (ESWs) reported in the literature. The key results are as follows: (i) compared to the effects of many other forms of therapy, the clinical benefit of ESWT does not appear to be based on a single mechanism; (ii) different tissues respond to the same mechanical stimulus in different ways; (iii) just because a mechanism of action of ESWT is described in a study does not automatically mean that this mechanism is relevant to the observed clinical effect; (iv) focused ESWs and radial ESWs seem to act in a similar way; and (v) even the most sophisticated research into the effects of exposure of musculoskeletal tissue to ESWs cannot substitute clinical research in order to determine the optimum intensity, treatment frequency and localization of ESWT.

Vasoactive Intestinal Peptide binds with high affinity to VPAC1R and VPAC2R, thus regulating key physiologic functions. Previously, we documented in VIP−/− mice a leaner body phenotype and altered metabolic hormones. Past reports described in VPAC2−/− mice impaired circadian rhythm, reduced food intake, and altered metabolism. To better define the effects of VPAC1R on body phenotype, energy/glucose homeostasis, and metabolism, we conducted a 12-week study in a VPAC1R null model. Our results reveal that VPAC1−/− mice experienced significant metabolic alterations during the dark cycle with greater numbers of feeding bouts (p = 0.009), lower Total Energy Expenditure (p = 0.025), VO2 (p = 0.029), and VCO2 (p = 0.016); as well as during the light cycle with lower Total Energy Expenditure (p = 0.04), VO2 (p = 0.044), and VCO2 (p = 0.029). Furthermore, VPAC1−/− mice had significantly higher levels of GLP-1 and PYY during fasting, and higher levels of GLP-1, glucagon leptin and PYY during postprandial conditions. In addition, VPAC1−/− mice had lower levels of glucose at 60′ and 120′, as assessed by insulin tolerance test. In conclusion, this study supports a key role for VPAC1R in the regulation of body glucose/energy homeostasis and metabolism.

People with insomnia frequently underestimate the duration of their sleep compared to objective polysomnography-measured sleep duration. Cognitive behavioural therapy for insomnia (CBT-I) is the most effective treatment for insomnia and also reduces the degree of sleep underestimation. Obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder characterised by frequent narrowing (hypopnoea) and closure (apnoea) of the upper airway during sleep. Comorbid insomnia and sleep apnoea (COMISA) is a prevalent and debilitating disorder. No study has investigated subjectively (sleep diary) versus objectively (polysomnography) measured sleep discrepancies (SOSD) in individuals with COMISA before or following CBT-I. This randomised waitlist-controlled trial investigated SOSD in 145 participants with COMISA before and 6-weeks after CBT-I (n = 72) versus control (n = 73). All participants were studied prior to continuous positive airway pressure treatment for sleep apnoea. At baseline, participants underestimated their total sleep time (mean ± SD −51.9 ± 94.1 min) and sleep efficiency (−9.6 ± 18.3%), and overestimated sleep onset latency (34.5 ± 86.1 min; all p = < 0.001). Mixed models indicated a main effect of time on reduction of SOSD in both groups, but no between-group difference in the reduction of any SOSD parameters. These findings may indicate that untreated OSA contributes to a discrepancy between perceived and objective sleep parameters in people with COMISA that is not amenable to CBT-I alone (ACTRN12613001178730).

Induction of vast transcriptional programs is a central event of innate host responses to viral infections. Here we report a transcriptional program with potent antiviral activity, driven by E74-like ETS transcription factor 1 (ELF1). Using microscopy to quantify viral infection over time, we found that ELF1 inhibits eight diverse RNA and DNA viruses after multi-cycle replication. Elf1 deficiency results in enhanced susceptibility to influenza A virus infections in mice. ELF1 does not feed-forward to induce interferons, and ELF1's antiviral effect is not abolished by the absence of STAT1 or by inhibition of JAK phosphorylation. Accordingly, comparative expression analyses by RNA-seq revealed that the ELF1 transcriptional program is distinct from interferon signatures. Thus, ELF1 provides an additional layer of the innate host response, independent from the action of type I interferons.

The rise of globalization in recent years has favored the adoption of unhealthy lifestyles for many people, increasing their likelihood of diseases with silent symptoms. Longevity spinach (Gynura procumbens L.) is a medicinal plant that has strong phenolic compounds which could act as natural antioxidants to reduce the chance of contracting severe silent diseases. This study was focused on the feasibility of an affordable herbal supplement manufacturing plant using longevity spinach with a water solvent. Production simulation was carried out using SuperPro Designer v.9.0, and an estimated annual production of 26,082 bottles was analyzed based on several economic parameters. The production process for herbal supplements from longevity spinach extract consisted of leaf-washing, drying, and grinding, as well as active compound extraction from leaves with water, filtration, evaporation, freeze-drying, and encapsulation. For 30 encapsulated herbal supplements, prices started from USD 22.8/bottle, and the designed production plant was economically feasible (PBP = ±17 months, IRR = 91.65%, and NPV = USD 3,972,653.13). It can be concluded that encapsulated longevity spinach water extract could become an affordable herbal supplement, with feasible manufacturing for further investment activity.

Summary: Sensory processing can be tuned by a neuron’s integration area, the types of inputs, and the proportion and number of connections with those inputs. Integration areas often vary topographically to sample space differentially across regions. Here, we highlight two visual circuits in which topographic changes in the postsynaptic retinal ganglion cell (RGC) dendritic territories and their presynaptic bipolar cell (BC) axonal territories are either matched or unmatched. Despite this difference, in both circuits, the proportion of inputs from each BC type, i.e., synaptic convergence between specific BCs and RGCs, remained constant across varying dendritic territory sizes. Furthermore, synapse density between BCs and RGCs was invariant across topography. Our results demonstrate a wiring design, likely engaging homotypic axonal tiling of BCs, that ensures consistency in synaptic convergence between specific BC types onto their target RGCs while enabling independent regulation of pre- and postsynaptic territory sizes and synapse number between cell pairs. : Yu et al. show that the density of excitatory synapses on retinal output neurons is invariant of retinal location, even though connectivity between pre- and postsynaptic cell pairs can vary. These results have implications for understanding topographic variations in processing of visual stimuli and for understanding consistency of CNS wiring diagrams.

Understanding how neurons encode and compute information is fundamental to our study of the brain, but opportunities for hands-on experience with neurophysiological techniques on live neurons are scarce in science education. Here, we present Spikeling, an open source in silico implementation of a spiking neuron that costs £25 and mimics a wide range of neuronal behaviours for classroom education and public neuroscience outreach. Spikeling is based on an Arduino microcontroller running the computationally efficient Izhikevich model of a spiking neuron. The microcontroller is connected to input ports that simulate synaptic excitation or inhibition, to dials controlling current injection and noise levels, to a photodiode that makes Spikeling light sensitive, and to a light-emitting diode (LED) and speaker that allows spikes to be seen and heard. Output ports provide access to variables such as membrane potential for recording in experiments or digital signals that can be used to excite other connected Spikelings. These features allow for the intuitive exploration of the function of neurons and networks mimicking electrophysiological experiments. We also report our experience of using Spikeling as a teaching tool for undergraduate and graduate neuroscience education in Nigeria and the United Kingdom.

Motion anticipation allows the visual system to compensate for the slow speed of phototransduction so that a moving object can be accurately located. This correction is already present in the signal that ganglion cells send from the retina but the biophysical mechanisms underlying this computation are not known. Here we demonstrate that motion anticipation is computed autonomously within the dendritic tree of each ganglion cell and relies on feedforward inhibition. The passive and non-linear interaction of excitatory and inhibitory synapses enables the somatic voltage to encode the actual position of a moving object instead of its delayed representation. General rather than specific features of the retinal connectome govern this computation: an excess of inhibitory inputs over excitatory, with both being randomly distributed, allows tracking of all directions of motion, while the average distance between inputs determines the object velocities that can be compensated for.

The visual system transmits information about fast and slow changes in light intensity through separate neural pathways. We used in vivo imaging to investigate how bipolar cells transmit these signals to the inner retina. We found that the volume of the synaptic terminal is an intrinsic property that contributes to different temporal filters. Individual cells transmit through multiple terminals varying in size, but smaller terminals generate faster and larger calcium transients to trigger vesicle release with higher initial gain, followed by more profound adaptation. Smaller terminals transmitted higher stimulus frequencies more effectively. Modeling global calcium dynamics triggering vesicle release indicated that variations in the volume of presynaptic compartments contribute directly to all these differences in response dynamics. These results indicate how one neuron can transmit different temporal components in the visual signal through synaptic terminals of varying geometries with different adaptational properties.