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Khoomei is a unique singing style originating from the Central Asian republic of Tuva. Singers produce two pitches simultaneously: a booming low-frequency rumble alongside a hovering high-pitched whistle-like tone. The biomechanics of this biphonation are not well-understood. Here, we use sound analysis, dynamic magnetic resonance imaging, and vocal tract modeling to demonstrate how biphonation is achieved by modulating vocal tract morphology. Tuvan singers show remarkable control in shaping their vocal tract to narrowly focus the harmonics (or overtones) emanating from their vocal cords. The biphonic sound is a combination of the fundamental pitch and a focused filter state, which is at the higher pitch (1-2 kHz) and formed by merging two formants, thereby greatly enhancing sound-production in a very narrow frequency range. Most importantly, we demonstrate that this biphonation is a phenomenon arising from linear filtering rather than a nonlinear source. Data is placed in four zipped files (compression done via Mac OS 10.12.4). The four files each contain a particular subset of the data: 1. Model.zip - Modeling software (Tube Talker) and several illustrative simulations 2. CroppedMRI_CB.zip - Both statis and dynamic MRI images (as .dcm files). Note that the DICOM files have been cropped (so to only show the relevant anatomical features) and metadata have been stripped. 3. SoundboothRecordings.zip - All soundbooth recordings, saved as .wav files (SR 96 kHz) 4. STL.zip - Reonstruction of the 3-D airspace, saved as a .stl file 5. MRIaudio.zip - Audio files collected during the MRI runs 6. MRImoviesC.zip - Movies of the dynamic data (with audio). Data is a combination of acoustical recordings, MRI data, and vocal tract modeling. Movie of the dynamic MRI data are also included. All details are included in the manuscript "Overtone focusing in biphonic Tuvan throat singing".

We introduce Sleep, a new Python open-source graphical user interface (GUI) dedicated to visualization, scoring and analyses of sleep data. Among its most prominent features are: (1) Dynamic display of polysomnographic data, spectrogram, hypnogram and topographic maps with several customizable parameters, (2) Implementation of several automatic detection of sleep features such as spindles, K-complexes, slow waves, and rapid eye movements (REM), (3) Implementation of practical signal processing tools such as re-referencing or filtering, and (4) Display of main descriptive statistics including publication-ready tables and figures. The software package supports loading and reading raw EEG data from standard file formats such as European Data Format, in addition to a range of commercial data formats. Most importantly, Sleep is built on top of the VisPy library, which provides GPU-based fast and high-level visualization. As a result, it is capable of efficiently handling and displaying large sleep datasets. Sleep is freely available (http://visbrain.org/sleep) and comes with sample datasets and an extensive documentation. Novel functionalities will continue to be added and open-science community efforts are expected to enhance the capacities of this module.

Objective: To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy. Methods: UX001-CL301 was a Phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE Myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6g/day or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by Upper Extremity Composite (UEC) score. Key secondary endpoints included change in Lower Extremity Composite (LEC) score, knee extensor strength, and GNE myopathy-Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results. Results: Eighty-nine patients were randomized (Ace-ER n = 45; Placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER -2.25 kg vs Placebo -2.99 kg; LSM difference (confidence interval [CI]) 0.74 (-1.61, 3.09); p = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) -1.49 (-5.83, 2.86); knee extension strength -0.40 (-2.38, 1.58); and GNEM-FAS mobility domain score -0.72 (-2.01, 0.57). Gastrointestinal events were the most common AEs. Conclusions: Ace-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy. Lochmuller et al UX001 CL301 MS supp materials protocol 13Dec2018Supplemental Material for Lochmuller et al Neurology: Table e-1. Change from Baseline to Week 48 in UEC and LEC Individual Muscle Groups with Hand-Held Dynamometry; Figure e-1. UX001-CL301 CONSORT Flow Diagram; UX001-CL301 Protocol

A central question in biology is how animals successfully behave under complex natural conditions. Although changes in locomotor behaviour, motor control and force production in relation to incline are commonly examined, a wide range of other factors, including a range of perch diameters, pervades arboreal habitats. Moving on different substrate diameters requires considerable alteration of body and limb posture, probably causing significant shifts in the lengths of the muscle–tendon units powering locomotion. Thus, how substrate shape impacts in vivo muscle function remains an important but neglected question in ecophysiology. Here, we used high-speed videography, electromyography, in situ contractile experiments and morphology to examine gastrocnemius muscle function during arboreal locomotion in the Cuban knight anole, Anolis equestris. The gastrocnemius contributes more to the propulsive effort on broad surfaces than on narrow surfaces. Surprisingly, substrate inclination affected the relationship between the maximum potential force and fibre recruitment; the trade-off that was present between these variables on horizontal surfaces became a positive relationship on inclined surfaces. Finally, the biarticular nature of the gastrocnemius allows it to generate force isometrically, regardless of substrate diameter and incline, despite the fact that the tendons are incapable of stretching during cyclical locomotion. Our results emphasize the importance of considering ecology and muscle function together, and the necessity of examining both mechanical and physiological properties of muscles to understand how animals move in their environment. Raw DataThis file contains the raw data used for generating all results for the manuscript. There are 6 sheets: Morphology contains the morphometric data for the hind limb and muscles for each individual; EMGdata contains all EMG variables used for analyses; HindlimbAngles contains all kinematic data of hind limb joint angles; HindlimbVelocities contains all kinematic data of hind limb joint angular velocities; ForceData contains values of potential force calculated for bursts and strides for each individual; and Force-LengthCurves contains the twitch force-length curves for the gastrocnemius muscles of each individual.dataForDryad.xlsx

Phenotypic integration patterns in the mammalian skull have long been a focus of intense interest as a result of their suspected influence on the trajectory of hominid evolution. Here we test the hypothesis that perturbation of cartilage growth, which directly affects only the chondrocranium during development, will produce coordinated shape changes in the adult calvarium and face regardless of mechanism. Using two murine models of cartilage undergrowth that target two very different mechanisms, we show that strong reduction in cartilage growth produces a short, wide, and more flexed cranial base. This in turn produces a short, wide face in both models. Cranial base and face are already correlated early in ontogeny, and the relationship between these modules gains structure through postnatal growth and development. These results provide further evidence that there exist physical interactions between developing parts of the phenotype that produce variation at a distance from the actual locus upon which a particular selective pressure is acting. Phenotypic changes observed over the course of evolution may not all require adaptationist explanations; rather, it is likely that a substantial portion of observed phenotypic variation over the history of a clade is not directly adaptive but rather a secondary consequence of some local response to selection. Adult Skull Landmark DataThis file contains raw landmark coordinates for adult mouse skulls.Adult.csvNeonatal Skull Landmark DataThis file contains raw landmark coordinates for neonatal mouse skulls.Neonatal.csv

Bluegill sunfish (Lepomis macrochirus) are one of the classic systems for studying male alternative reproductive tactics (ARTs) in teleost fishes. In this species, there are two distinct life histories: parental and cuckolder, encompassing three reproductive tactics, parental, satellite, and sneaker. The parental life history is fixed, whereas individuals who enter the cuckolder life history transition from sneaker to satellite tactic as they grow. For this study, we used RNAseq to characterize the brain transcriptome of the three male tactics and females during spawning to identify gene ontology (GO) categories and potential candidate genes associated with each tactic. We found that sneaker males had higher levels of gene expression differentiation compared to the other two male tactics. Sneaker males also had higher expression in ionotropic glutamate receptor genes, specifically AMPA receptors, compared to other males, which may be important for increased spatial working memory while attempting to cuckold parental males at their nests. Larger differences in gene expression also occurred among male tactics than between males and females. We found significant expression differences in several candidate genes that were previously identified in other species with ARTs and suggest a previously undescribed role for cAMP-responsive element modulator (crem) in influencing parental male behaviors during spawning. Fish sampling informationA text file detailing sampling information for fish used in this study. It includes the sex, tactic, total and standard length, sampling colony, sampling location, and RNA integrity numbers.Fish_sampling_info.txtTranscript CountsRaw transcripts counts produced from eXpress for all samplesMerged.results.xprsR scriptContains the R scripts used with edgeR for differential gene expression analysisRscript_DE_Analysis.txtAssembled transcriptomeAssembled bluegill transcriptome. Assembled de novo using Trinity.bluegill.final.fa

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, and white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air–tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental setup for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains.

The mammalian MRI (MaMI) data set is a comprehensive database that encompasses high-resolution ex vivo diffusion and structural (T1- and T2-weighted) MRI scans of 124 mammalian species, and a total of 225 scans including replicas. This data set was originally used by Yaniv Assaf (Assaf, Y. et al., 2020, Nat. Neurosci.; doi: https://doi.org/10.1038/s41593-020-0641-7). The version of the data set included in this repository only includes the network matrices obtained from the MRI scans. Details on the preprocessing of the data and the reconstruction of the matrices can be found in Suarez, LE. et al., 2022, bioRxiv; doi: https://doi.org/10.1101/2022.03.11.483995.

Open ocean surface CO2 levels are projected to reach approximately 800 µatm, and ocean pH to decrease by approximately 0.3 units by the year 2100 due to anthropogenic CO2 emissions and the subsequent process of ocean acidification (OA). When exposed to these CO2/pH values, several fish species display abnormal behaviour in laboratory tests, an effect proposed to be linked to altered neuronal GABAA receptor function. Juvenile blacksmith (Chromis punctipinnis) are social fish that regularly experience CO2/pH fluctuations through kelp forest diurnal primary production and upwelling events, so we hypothesized that they might be resilient to OA. Blacksmiths were exposed to control conditions (pH 7.92; pCO2 540 µatm), constant acidification (pH 7.71; pCO2 921 µatm) and oscillating acidification (pH 7.91, pCO2 560 µatm (day), pH 7.70, pCO2 955 µatm (night)), and caught and tested in two seasons of the year when the ocean temperature was different: winter (16.5 ± 0.1°C) and summer (23.1 ± 0.1°C). Neither constant nor oscillating CO2-induced acidification affected blacksmith individual light/dark preference, inter-individual distance in a shoal or the shoal's response to a novel object, suggesting that blacksmiths are tolerant to projected future OA conditions. However, blacksmiths tested during the winter demonstrated significantly higher dark preference in the individual light/dark preference test, thus confirming season and/or water temperature as relevant factors to consider in behavioural tests. In order to allow full comparability with other ocean acidification data sets, the R package seacarb (Gattuso et al, 2022) was used to compute a complete and consistent set of carbonate system variables, as described by Nisumaa et al. (2010). In this dataset the original values were archived in addition with the recalculated parameters (see related PI). The date of carbonate chemistry calculation by seacarb is 2023-05-15.