Miracle-dz/UniFAR-FTUs huggingface dataset:
Addition of new neurons and the emergence of a local neural circuit for precise timing

During development, neurons arrive at local brain areas in extended period of time, but how they form local neural circuits is unknown. Here we computationally model the emergence of a network for precise timing in the premotor nucleus HVC in songbird. We show that new motor projection neurons, mostly added to HVC before and during song learning, are recruited to the end of a growing feedforward network. High spontaneous activity of new neurons makes them the prime targets for recruitment in a self-organized process via synaptic plasticity. Once recruited, the new neurons fire readily at precise times, and they become mature. Neurons that are not recruited become silent and replaced by new immature neurons. Our model incorporates realistic HVC features such as interneurons, spatial distributions of neurons, and distributed axonal delays. The model predicts that the birth order of the projection neurons correlates with their burst timing during the song. Significance Statement Functions of local neural circuits depend on their specific network structures, but how the networks are wired is unknown. We show that such structures can emerge during development through a self-organized process, during which the network is wired by neuron-by-neuron recruitment. This growth is facilitated by steady supply of immature neurons, which are highly excitable and plastic. We suggest that neuron maturation dynamics is an integral part of constructing local neural circuits.
SUMOylation of rice DELLA SLR1 modulates transcriptional responses and improves yield under salt stress

DELLA proteins modulate GA signalling and are major regulators of plant plasticity to endure stress. DELLAs are mostly regulated at the post-translational level, and their activity relies on the interaction with upstream regulators and transcription factors (TFs). SUMOylation is a post-translational modification (PTM) capable of changing protein interaction and found to influence DELLA activity in Arabidopsis. We determined that SUMOylation of the single rice DELLA SLENDER RICE1 (SLR1) occurs in a lysine residue different from the one previously identified in Arabidopsis REPRESSOR OF GA (RGA). Remarkably, artificially increasing SUMOylated SLR1 (SUMO1SLR1) levels attenuated the penalty of salt stress on plant yield. Gene expression analysis revealed that the overexpression of SUMOylated SLR1 regulates key dioxygenases that modulate active GA levels, namely GA20ox2 and GA2ox3, which could partially explain the sustained productivity upon salt stress imposition. Besides, SLR1 SUMOylation blocked the interaction with the growth regulator YAB4, which may fine-tune GA20ox2 expression. Mechanistically, we propose that SLR1 SUMOylation disrupts the interaction with members of several transcription factor families to modulate gene expression. We found that SLR1 SUMOylation represents a novel mechanism modulating DELLA activity, which attenuates the impact of stress on plant performance. One sentence summary Rice plants show increased yield under salt stress when its gibberellin transcriptional regulator DELLA protein is artificially SUMOylated.
A Clock-Driven Neural Network Critical for Arousal

The daily cycling of sleep and arousal states are among the most prominent biological rhythms under circadian control. While much is known about the core circadian clock1,2, how this clock regulates sleep and arousal remains poorly understood3. In Drosophila, we previously characterized WIDE AWAKE (WAKE), a clock-output molecule that promotes sleep at night4,5. Here, we show that the function of WAKE is conserved in mice and that mWAKE+ neurons comprise a clock-regulated arousal system. Besides the suprachiasmatic nucleus (SCN), mWAKE is expressed in the dorsomedial hypothalamus (DMH) and other arousal-related regions. mWAKE mutants exhibit increased spiking of mWAKE+ neurons and increased behavioural arousal at night. In the DMH, mWAKE labels a novel circuit that promotes wakefulness and is required for rapid eye-movement sleep. Single-cell sequencing, immunostaining, and patch-clamp experiments reveal that mWAKE+ neurons constitute a glutamatergic/gabaergic population that projects widely, receives neuromodulatory input, and acts on neuromodulatory neurons. Strikingly, broad chemogenetic silencing of mWAKE+ cells leads to profound loss of behavioural responsiveness and low amplitude, low frequency electroencephalography waveforms. These findings suggest that the genetic mechanisms regulating circadian control of sleep and arousal are conserved across >500 million years of evolution and define a clock-regulated neural network critical for arousal.
A numerical study about the flight of the dragonfly: 2D gliding and 3D hovering regimes

The dragonfly’s ability of gliding and performing dexterous maneuvers during flight attracts the interest of scientists and engineers who aim at replicating its performances in micro air vehicles. The great efficiency of its flight is achieved thanks to the vortices generated by wing movements and thanks to the corrugations on their surfaces. The high freedom of control of each wing has been proved to be the secret behind the dragonfly capability to carry out incredible flight manoeuvers. The study presented in this paper analyzes two of the most common flight regimes of the dragonfly. Firstly, some CFD simulations of gliding are performed and drag and lift coefficients have been calculated, showing a good match with experimental data found in literature. Then, hovering has been studied using a methodology inspired to the Blade Element Momentum (BEM) theory, which is usually applied in the context of wind turbines design. The lift force calculated with this simulation corresponds to the weight of dragonfly, suggesting the correctness of this analysis.
Cofilin loss in Drosophila contributes to myopathy through defective sarcomerogenesis and aggregate formation during muscle growth

Sarcomeres, the fundamental contractile units of muscles, are conserved structures composed of actin thin filaments and myosin thick filaments. How sarcomeres are formed and maintained is not well understood. Here, we show that knockdown of Drosophila Cofilin (DmCFL), an actin depolymerizing factor, leads to the progressive disruption of sarcomere structure and muscle function in vivo. Loss of DmCFL also results in the formation of sarcomeric protein aggregates and impairs sarcomere addition during growth. Strikingly, activation of the proteasome delayed muscle deterioration in our model. Further, we investigate how a point mutation in CFL2 that causes nemaline myopathy (NM) in humans, affects CFL function and leads to the muscle phenotypes observed in vivo. Our data provide significant insights to the role of CFLs during sarcomere formation as well as mechanistic implications for disease progression in NM patients.
Investigating the effects eight weeks of non-continuous aerobic exercise on the levels of angiopoietin2-like protein and interferon beta in rats suffering from coronary artery disease

Background: Reviewing the previous studies reveals that the balance between stimulators and inhibitors of angiogenesis is of a great deal of importance. Among these factors, it can be pointed to the ANGPT2-like protein and the interferon (IFN)-beta. Since hypoxia is one of the most powerful stimulators of angiogenesis and considering the fact that endurance training creates a hypoxia condition. Aims and Objectives: The purpose of the present study was to investigate the effects of 8 weeks of noncontinuous aerobic exercise on levels of angiopoietin2-like proteins and IFN beta (IFNβ) in male rats suffering from coronary artery disease. Materials and Methods: To this end, 32 months old rats weighting between 200 and 250 g were randomly selected. Afterward, 20 of the rats were made sick and further divided into two 10 member groups of control and experimental. The experimental group received 5 sessions of non-continuous aerobic exercises on animal per week for 8 weeks on an animal treadmill while the control group did not receive any exercises during these 8 weeks. After the period of the experiment, 5 mL of blood was taken from reach rat�s lower inferior vein 72 h after the past exercise after anesthetization by expert animal surgeons. Research data have been analyzed using the ANOVA test and the SPSS v.0. 24 Software. Results: Research findings indicate that after 8 weeks of participation in non-continuous aerobic exercises, a certain statistically significant difference was made between the control and experimental groups in terms of the level of IFNβ. However, no statistically significant difference was recorded for the level of angiopoitein-2 like proteins. Conclusion: In general and with respect to the obtained results it can be stated that 8 weeks of non-continuous aerobic exercises did not result in an increase in the angiopoietin-2 like proteins level while resulting in a statistically significant decrease in the level of IFNβ.
Onset, Time to Recurrence, and Recurrence Risk Factors of Myocardial Infarction and Ischemic Stroke: 10-Year Nationwide one-Million Population Database

Background and Purpose We aimed to determine the differences in the pathophysiology of myocardial infarction (MI) and ischemic stroke (IS) and present their basic epidemiologic data for public health policy. Methods We included patients with a history of admission with diagnostic codes of MI and IS in the National Health Information Database (NHID) of the National Health Insurance Service (NHIS) Sample Cohort 2002-2013. We investigated the time to primary and secondary events, difference in incidence based on sex, time interval for the secondary event following the primary event in MI and IS, and the relative risk of recurrent events compared with that of primary events. Results The mean age of onset of IS was significantly higher than that of MI (65.67±12.25 vs. 60.4±13.07 years; P<0.05). The mean period from primary IS to secondary IS was significantly shorter than that from primary IS to secondary MI (2.09±2.80 vs. 5.35±2.90 years; P=0.016). The mean period from primary MI to secondary MI was significantly shorter than that from primary MI to secondary IS (2.30±2.75 vs. 5.16±3.26 years; P<0.001). The incidence of IS in men was significantly higher than that in women. The relative risk of recurrent IS and MI was greater than that of the primary event. In patients younger than 70 years, the incidence of MI was higher than that of IS, while in those above 70 years it was lower (P<0.05). Conclusions The age at onset, time to recurrence, sex, and relative risks are significantly different between ischemic stroke and myocardial infarction, suggesting that the underlying pathophysiologic mechanisms might be different between the two.
State Dependent Beta Oscillations in the Cortico-Basal Ganglia Circuit and their Neuromodulation under Phase-Locked Inputs

State-of-the-art therapeutic brain stimulation strategies are delivered open loop, using fixed parameters. However, brain states exhibit spontaneous fluctuations dependent upon different behavioural or disease states. Here, we use a model of the cortico-basal ganglia-thalamic circuit to demonstrate how connectivity underpins changes in subcortical beta oscillations – a commonly used control parameter for deep brain stimulation in Parkinson’s disease. We show that recurrent cortical-subcortical loops involving either the cortico-subthalamic or pallido-subthalamic pathways can act in antagonism to modulate the expression of beta band activity (14-30 Hz). These pathways alter the relative timing of intermittent activity across the network, with increased pallido-subthalamic connectivity increasing the propensity of the circuit to enter a state of autonomous oscillation. We demonstrate that phase-locked stimulation can modulate these oscillations, with an efficacy that ultimately depends upon the connectivity across the circuit. This work outlines critical factors required to implement state-adaptive closed-loop brain stimulation. Highlights Converging inputs to the subthalamic nucleus arriving via the external segment of globus pallidus and cortex act in antagonism and promote different beta rhythms. Phase locked stimulation has the capacity to selectively enhance or suppress a brain rhythm depending on the stimulation timing. The efficacy of stimulation and the parameters required to deliver it, e.g. stimulation timing, effective sensing and stimulation locations, are functions of network state.
In response to Li et al.: Linker histones function in Drosophila embryogenesis

In an earlier paper (Pérez-Montero et al., 2013), we reported that the embryonic linker histone of Drosophila dBigH1 was essential for early Drosophila embryogenesis since embryos homozygous for the bigH1100 mutation showed strong defects and did not survive beyond zygotic genome activation (ZGA) at cellularization. Recent results challenge these observations since null bigH1 mutations generated by CRISPR/Cas9 methodology turn out to be homozygous viable, as reported in Li et al. (2019) and here. In this regard, Li et al. described a novel mechanism by which lack of dBigH1 is compensated by the early expression of maternal dH1. Here, we confirm this observation and show that such compensatory mechanism is not activated in bigH1100 embryos.
Auxin Regulation and MdPIN Expression during Adventitious Root Initiation in Apple Cuttings

Adventitious root (AR) formation is critical for the efficient propagation of elite horticultural and forestry crops. Despite decades of research, the cellular processes and molecular mechanisms underlying AR induction in woody plants remains obscure. We examined the details of AR formation in the apple (Malus domestica) M.9 rootstock, the most widely used dwarf rootstock for intensive production, and investigated the role of polar auxin transport in post-embryonic organogenesis. AR formation begins with a series of founder cell divisions and elongation of interfascicular cambium adjacent to vascular tissues. This process was associated with a relatively high indole acetic acid (IAA) content and hydrolysis of starch grains. Exogenous auxin treatment promoted cell division, as well as the proliferation and reorganization of the endoplasmic reticulum and Golgi membrane. By contrast, treatment with the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA) inhibited cell division in the basal region of the cutting and resulted in abnormal cell divisions during early AR formation. In addition, PIN-FORMED (PIN) transcripts were expressed differentially throughout the whole AR development process, with the up-regulation of MdPIN8 and MdPIN10 during induction, an up-regulation of MdPIN4, MdPIN5 and MdPIN8 during extension, and an up-regulation of all MdPINs during AR initiation. This research provides a deeper understanding of the cellular and molecular underpinnings of the AR process in woody plants.
Laminin-511 and α6 integrins regulate the expression of CXCR4 to promote endothelial morphogenesis.

During angiogenesis, endothelial cells engage components of the extracellular matrix through integrin-mediated adhesion. Endothelial expression of laminin-411 and laminin-511 are known to promote vessel stability. However, little is known about the contribution of these laminins to endothelial morphogenesis. We used two organotypic cell culture angiogenesis assays in conjunction with RNAi approaches to demonstrate that depletion of either the α4 chain of laminin-411 or the α5 chain of laminin-511 from endothelial cells inhibits sprouting and tube formation. Depletion of α6 integrins resulted in similar phenotypes. Gene expression analysis indicated that loss of either laminin-511 or α6 integrins inhibited the expression of CXCR4, a gene previously associated with angiogenic endothelial cells. Pharmacological or RNAi-dependent inhibition of CXCR4 suppressed endothelial sprouting and morphogenesis. Importantly, expression of recombinant CXCR4 rescued endothelial morphogenesis when the α6 integrin expression was inhibited. Additionally, the depletion of α6 integrins from established tubes resulted in the loss of tube integrity and laminin-511. Taken together, our results indicate that α6 integrins and laminin-511 can promote endothelial morphogenesis by regulating the expression of CXCR4 and suggest that the α6-dependent deposition of laminin-511 protects the integrity of established endothelial tubes.
Genetic analysis identifies the Ostrea stentina/aupouria/equestris oyster species complex in Hawai‘i, and resolves its lineage as the western Pacific O. equestris

Background Extensive phenotypic plasticity in oysters makes them difficult to identify based on morphology alone, but their identities can be resolved by applying genetic and genomic technologies. In this study, we collected unknown oyster specimens from Hawaiian waters for genetic identification. Methods We sequenced two partial gene fragments, mitochondrial 16S ribosomal RNA (16S) and cytochrome c oxidase subunit I (COI), in 48 samples: 27 unidentified oyster specimens collected from two locations on O‘ahu, 13 known specimens from a hatchery in Hilo, Hawai‘i Island, and 8 known specimens from Hilo Bay, Hawai‘i Island. Results Molecular data identified approximately 85% of unknown samples as belonging to the Ostrea stentina/aupouria/equestris species complex, a globally distributed group with a history of uncertain and controversial taxonomic status. The remaining unknown samples were the native Dendostrea sandvichensis (G. B. Sowerby II, 1871), and nonnative Crassostrea gigas (Thunberg, 1793), the latter of which is a commercial species that was introduced to Hawai‘I from multiple sources during the 20th century. Phylogenetic analysis placed Hawai‘i Ostrea alongside samples from China, Japan, and New Zealand, grouping them within the recently classified western Pacific O. equestris. Until now, four extant species of true oyster have been documented in Hawai‘i. This study expands the known range of O. equestris by providing the first verification of its occurrence in Hawai‘i.
Living with a Stoma After Surgical Resection for Rectal Cancer: An Interpretive Phenomenological Study to Understand How Stomas Can Affect Physical Activity

Purpose: Rising survival rates suggest adults must increasingly cope with the adverse effects of cancer and its treatments, which may limit their participation in health-enhancing behaviours such as physical activity. Furthermore, the placement of a stoma may cause additional challenges to being physically active. This study aimed to explore the experience of rectal cancer survivors who were living with a stoma and the impact this has on their participation in physical activity. Methods: This study followed an interpretive phenomenological analysis (IPA) to provide detailed examinations of 15 rectal cancer survivors’ personal lived experience. Participants took part in a semi-structured interview post-chemotherapy. Results: Three themes captured participants’ personal lived experience: (1) understanding the drive and motivation to be physically active, (2) despite being motivated to be physically active with a stoma, it can be challenging, and (3) how to be physically active: lessons learned. Conclusions: Participants’ accounts offered insight into the motivating and challenging experiences they faced from cancer and its treatments. Implications for cancer survivors: Current programs and services offered for cancer survivors to be more physically active may neglect the needs of those who have a stoma from cancer. Integrating cancer-specific needs with strategies discussed by study participants may better support cancer survivors’ choice to be physically active, thus improving their quality of life after cancer.
Global gut content data synthesis and phylogeny delineate reef fish trophic guilds

The diversity of life on our planet has produced a remarkable variety of biological traits that characterize different species. Such traits are widely employed instead of taxonomy to increase our understanding of biodiversity and ecosystem functioning. However, for species’ trophic niches, one of the most critical aspects of organismal ecology, a paucity of empirical information has led to inconsistent definitions of trophic guilds based on expert opinion. Using coral reef fishes as a model, we show that experts often disagree on the assignment of trophic guilds for the same species. Even when broad categories are assigned, 60% of the evaluated trait schemes disagree on the attribution of trophic categories for at least 20% of the species. This disagreement greatly hampers comparability across studies. Here, we introduce a quantitative, unbiased, and fully reproducible framework to define species’ trophic guilds based on empirical data. First, we synthesize data from community-wide visual gut content analysis of tropical coral reef fishes, resulting in trophic information from 13,961 individuals belonging to 615 reef fish species across all ocean basins. We then use network analysis to cluster the resulting global bipartite food web into distinct trophic guilds, resulting in eight trophic guilds, and employ a Bayesian phylogenetic model to predict trophic guilds based on phylogeny and maximum body size. Our model achieved a misclassification error of 5%, indicating that our approach results in a quantitative and reproducible trophic categorization scheme, which can be updated as new information becomes available. Although our case study is for reef fishes, the most diverse vertebrate consumer group, our approach can be applied to other organismal groups to advance reproducibility in trait-based ecology. As such, our work provides an empirical and conceptual advancement for trait-based ecology and a viable approach to monitor ecosystem functioning in our changing world.
Triggering mechanisms for motor actions: A mini meta-analysis and experimental data

Motor actions can be released much sooner than normal when the go-signal is of very high intensity (> 100dBa). Although statistical evidence from individual studies has been mixed, it has been assumed that sternocleidomastoid (SCM) muscle activity could be used to distinguish between two neural circuits involved in movement triggering. We summarized meta-analytically the available evidence for this hypothesis, comparing the difference in premotor reaction time (RT) of actions where SCM activity was elicited (SCM+ trials) by loud acoustic stimuli against trials in which it was absent (SCM- trials). We found ten studies, all reporting comparisons between SCM+ and SCM- trials. Our mini meta-analysis showed that premotor RTs are faster in SCM+ than in SCM- trials. We also present experimental data showing the effects of foreperiod predictability can induce differences in RT that would be of similar size to those attributed to the activation of different neurophysiological pathways to trigger prepared actions. We discuss plausible physiological mechanisms that would explain differences in premotor RTs between SCM+ and SCM-trials.