Miracle-dz/UniFAR-FTUs huggingface dataset:
Model-free analysis in the spectral domain of postmortem mouse brain EPSI reveals inconsistencies with model-based analyses of the free induction decay

Purpose Dysmyelinating disorders lead to abnormalities in myelin structure that produce detectable effects in an echo-planar spectroscopic imaging (EPSI) signal. To estimate the voxel-wise proportion of myelin, data are typically fit to compartmental models in the time domain. This work characterizes limitations in these models by comparing high-resolution water spectra measured in postmortem fixed mouse brains to spectra predicted from time-domain models fit to the same data, specifically by comparing spectra from control and shiverer mice, a model for dysmyelination. Methods Perfusion-fixed, resected control (n = 5) and shiverer (n = 4) mouse brains were imaged using 3D EPSI with 100 µm isotropic resolution. The free induction decay (FID) was sampled every 2.74 ms over 192 echoes and Fourier transformed to produce water spectra with 1.9 Hz resolution. FIDs were also fit to two biophysical models and the resulting fits were converted to spectra with a Fourier transform. Spectral asymmetry was computed and compared before and after fitting the data to models. Results Spectra derived from both models did not show the magnitude of asymmetric broadening observed in the raw data. Correlations between data- and model-derived asymmetries and estimated frequency shifts are weak, leading to a reduction in spectral sensitivity to changes in white-matter structure after fitting the data to models. Conclusion The results demonstrate spectral inconsistencies between biophysical model predictions and measured data, promoting the further incorporation of spectral analysis methods to develop and benchmark new model-based approaches.
Cortical compensation for afferent loss in older adults: Associations with GABA and speech recognition in noise

Age-related deficits in auditory nerve (AN) function reduce afferent input to the auditory cortex. The extent to which the auditory cortex in older adults compensates for this loss of afferent input, also known as central gain, and the mechanisms underlying this compensation are not well understood. We took a neural systems approach to estimate central gain, measuring AN and cortical evoked responses within 50 older and 27 younger adults. Amplitudes were significantly smaller for older than for younger adults for AN responses but not for cortical responses. We used the relationship between AN and cortical response amplitudes in younger adults to predict cortical response amplitudes for older adults from their AN responses. Central gain in older adults was thus defined as the difference between their observed cortical responses and those predicted from the parameter estimates of younger adults. More central gain was associated with decreased cortical levels of GABA measured with 1H-MRS and poorer speech recognition in noise (SIN). Effects of central gain and GABA on SIN occur in addition to, and independent from, effects attributed to elevated hearing thresholds. Our results are consistent with animal models of central gain and suggest that reduced AN afferent input in some older adults may result in changes in cortical encoding and inhibitory neurotransmission, which contribute to reduced SIN. An advancement in our understanding of the changes that occur throughout the auditory system in response to the gradual loss of input with increasing age may provide potential therapeutic targets for intervention. Significance Age-related hearing loss is one of the most common chronic conditions of aging, yet little is known about how the cortex compensates for this loss of sensory input. We measured AN and cortical responses to the same stimulus in younger and older adults. In older adults we found an increase in cortical activity following concomitant declines in afferent input that are consistent with central gain. Increased central gain was associated with lower levels of cortical GABA, an inhibitory neurotransmitter, which predicted poorer speech recognition in noise. The results suggest that the cortex in older adults can compensate for attenuated sensory input by reducing inhibition to amplify the cortical response, but this amplification may lead to poorer speech recognition in noise.
Load Non-Linearly Modulates Movement Reflex Gain in an Insect Leg via a Distributed Network of Identified Nonspiking Interneurons

Producing context-specific motor acts requires sensorimotor neural networks to integrate multiple sensory modalities. Some of this integration occurs via presynaptic interactions between proprioceptive afferent neurons themselves,1,2 other by afferents of different modalities targeting appropriate motor neurons (MNs). 3–5 How the interneuronal network typically interposed between sensory afferents and MNs contributes to this integration, particularly at single-neuron resolution, is much less understood. In stick insects, this network contains nonspiking interneurons (NSIs) converging onto the posture-controlling slow extensor tibiae motor neuron (SETi). We analyzed how load altered movement signal processing by tracing the interaction of movement (femoral chordotonal organ, fCO) and load (tibial campaniform sensilla, tiCS) signals from the afferents through the NSI network to the motor output. On the afferent level, load reduced movement signal gain by presynaptic inhibition; tiCS stimulation elicited primary afferent depolarization and reduced fCO afferent action potential amplitude. In the NSI network, graded responses to movement and load inputs summed nonlinearly and increased the gain of NSIs opposing movement-induced reflexes. The gain of SETi and muscle movement reflex responses consequently decreased. Gain modulation was movement parameter-specific and required presynaptic inhibition; pharmacologically blocking presynaptic inhibition abolished load-dependent tuning of SETi responses. These data describe sensorimotor gain control at the sensory, premotor, and motor levels. Presynaptic inhibition-mediated nonlinear integration allowed the NSI network to respond to movement sensory input in a context (load)-dependent manner. These findings show how gain changes can allow premotor networks to integrate multiple sensory modalities and thus generate context-appropriate motor activity.
The impacts of transfer learning, phylogenetic distance, and sample size on big-data 1 bioacoustics 2

: 12 Vocalizations in animals, particularly birds, are critically important behaviors that influence their 13 reproductive fitness, but automatically extracting vocalization data from existing large databases 14 has only recently gained traction and has yet to be evaluated with respect to accuracy of different 15 approaches. Here, we use a recently-published machine learning framework to extract syllables 16 from six bird species ranging in their phylogenetic relatedness from 1–85 million years, 17 comparing how phylogenetic relatedness impacts accuracy as well as the utility of applying 18 trained models to novel species. Model performance is best on conspecifics, with accuracy 19 progressively decreasing as phylogenetic distance increases between taxa; however, using 20 models trained on multiple distantly related species can recover the lost accuracy. When 21 planning big-data bioacoustics studies, care must be taken in sample design to maximize sample 22 size and minimize human labor without sacrificing accuracy. 23
Association Mapping Across a Multitude of Traits Collected in Diverse Environments Identifies Pleiotropic Loci in Maize

Classical genetic studies have identified many cases of pleiotropy where mutations in individual genes alter many different phenotypes. Quantitative genetic studies of natural genetic variants frequently examine one or a few traits, limiting their potential to identify pleiotropic effects of natural genetic variants. Widely adopted community association panels have been employed by plant genetics communities to study the genetic basis of naturally occurring phenotypic variation in a wide range of traits. High-density genetic marker data – 18M markers – from two partially overlapping maize association panels comprising 1,014 unique genotypes grown in field trials across at least seven US states and scored for 162 distinct trait datasets enabled the identification of of 2,154 suggestive marker-trait associations and 697 confident associations in the maize genome using a resampling-based genome-wide association strategy. The precision of individual marker-trait associations was estimated to be three genes based a reference set of genes with known phenotypes. Examples were observed of both genetic loci associated with variation in diverse traits (e.g. above-ground and below-ground traits), as well as individual loci associated with the same or similar traits across diverse environments. Many significant signals are located near genes whose functions were previously entirely unknown or estimated purely via functional data on homologs. This study demonstrates the potential of mining community association panel data using new higher density genetic marker sets combined with resampling-based genome-wide association tests to develop testable hypotheses about gene functions, identify potential pleiotropic effects of natural genetic variants, and study genotype by environment interaction.
Coronavirus Disease 2019 Safety Measures for Sustainable Tourism: The Mediating Effect of Tourist Trust

Coronavirus disease 2019 (COVID-19) pandemic is continuing to have severe effects on tourism-related industries, as safety precautions have become essential to follow. Based on this, this study aims to explore the role of perceptions of the tourist of safety in tourism destination choice with the mediating effect of tourist trust (TT) in the context of the Chinese tourism sector. In addition, this study considers improvements to safety measures for sustainable tourism and the benefits of the technology transformation in the travel industry because of COVID-19. For this study, a quantitative approach was used, and data were collected through convenient sampling. The questionnaire was measured on a 5-point Likert scale, and a cross-sectional approach was adopted for data analysis. The findings of this study show that the effect of the perceived safety of the social environment, perceived safety of facility and equipment elements, perceived safety of human elements, perceived safety of management elements, and perceived safety of natural environments is significant and positive on the tourist destination choice (TDC). In addition, TT is a significant mediator between these elements and TDC. Furthermore, this study concluded that COVID-19 had increased travel anxiety, with particularly negative effects on the Chinese tourism sector, but that the adoption of perceived safety measures could be beneficial in regaining TT for traveling, eventually giving tourists confidence in choosing their traveling destination.
Clinical Significance of Volume Status in Body Composition and Physical Performance Measurements in Hemodialysis Patients

Introduction This study aimed to evaluate the association between volume status and body composition or physical performance measurements in hemodialysis patients. Methods A total of 84 patients were enrolled in this study. The participants were divided into tertiles based on the edema index (extracellular water/total body water): low, middle, and high tertiles. Serum albumin and serum high-sensitivity C-reactive protein levels were measured. The appendicular lean mass index (ALM/Ht2, kg/m2) was measured using dual-energy X-ray absorptiometry. The thigh muscle area index (TMA/Ht2, cm2/m2) was measured using CT. Extracellular and total body water and phase angles were obtained using bioimpedance analysis. The results of the subjective global assessment (SGA), hand-grip strength (HGS), gait speed (GS), short physical performance battery (SPPB), sit-to-stand for 30-second (STS30) test, timed up and go (TUG), sit-to-stand test performed five times (STS5), and 6-minute walk (6-MW) tests were also evaluated. Results On the univariate analysis, the SGA score and phase angle in the high tertile group were the lowest among the three groups. On multivariate analysis, TMA/Ht2 and phase angle in the high tertile were the lowest among the three groups. Inverse correlations were observed between edema index and TMA/Ht2, SGA score, phase angle, HGS, GS, SPPB, STS30, or 6-MW. Positive correlations were observed between the edema index and the STS5 or TUG test. The sensitivity and specificity for predicting low GS were 34.5 and 89.7%, respectively. The values for predicting low SPPB were 68.0 and 79.7%, respectively. Conclusion This study demonstrates that high volume status may be associated with decreased muscle mass and physical performance regardless of inflammatory or nutritional status.
Activation of CNR1/PI3K/AKT Pathway by Tanshinone IIA Protects Hippocampal Neurons and Ameliorates Sleep Deprivation-Induced Cognitive Dysfunction in Rats

Sleep deprivation is commonplace in modern society, Short periods of continuous sleep deprivation (SD) may negatively affect brain and behavioral function and may lead to vehicle accidents and medical errors. Tanshinone IIA (Tan IIA) is an important lipid-soluble component of Salvia miltiorrhiza, which could exert neuroprotective effects. The aim of this study was to investigate the mechanism of neuroprotective effect of Tan IIA on acute sleep deprivation-induced cognitive dysfunction in rats. Tan IIA ameliorated behavioral abnormalities in sleep deprived rats, enhanced behavioral performance in WMW and NOR experiments, increased hippocampal dendritic spine density, and attenuated atrophic loss of hippocampal neurons. Tan IIA enhanced the expression of CB1, PI3K, AKT, STAT3 in rat hippocampus and down-regulated the expression ratio of Bax to Bcl-2. These effects were inhibited by cannabinoid receptor 1 antagonist (AM251). In conclusion, Tan IIA can play a neuroprotective role by activating the CNR1/PI3K/AKT signaling pathway to antagonize apoptosis in the hippocampus and improve sleep deprivation-induced spatial recognition and learning memory dysfunction in rats. Our study suggests that Tan IIA may be a candidate for the prevention of sleep deprivation-induced dysfunction in spatial recognition and learning memory.
Effects of Saccharomyces Cerevisiae Cultures on Performance and Immune Performance of Dairy Cows During Heat Stress

The dairy farming industry is facing massive economic losses as heat stress continues to rise. The purpose of this study was to see how feeding Saccharomyces cerevisiae culture (SC) influences productive performance, lactation performance, serum biochemical indexes, hormonal level, antioxidant capacity, and immune function in mid-lactating cows during heat stress. Forty-five healthy mid-lactation dairy cows with comparable milk yield, lactation days, and parity were randomly divided into 3 groups (15 cows in each group). The control group (CON) was fed the basal diet, while the treatment groups were fed the basal diet + first Saccharomyces cerevisiae culture 100 g/d (SC-1) and the basal diet + second Saccharomyces cerevisiae culture 30 g/d (SC-2), respectively. The SC-1 and SC-2 groups with SC added in the treatment groups reduced rectal temperature and respiratory rate in heat-stressed cows (P < 0.05). The milk yield of SC-1 and SC-2 treatment groups was significantly higher than that of CON (P < 0.05). Except for somatic cell count, which was significantly lower in SC-1 and SC-2 than in CON (P < 0.05), there were no significant differences in the milk components. The addition of SC: (i) increased serum urea levels (P < 0.05), but there was no significant difference in glucose, total cholesterol, alanine transaminase, aspartate aminotransferase, total protein, albumin and alkaline phosphatase levels (P > 0.05); (ii) increased serum levels of immunoglobulin-A, immunoglobulin-G, immunoglobulin M, interleukin-4, interleukin-10 and heat shock protein-70 (P < 0.05), while decreasing serum levels of interleukin-1β, interleukin-6, interleukin-2, interferon-γ and tumor necrosis factor-α (P < 0.05); (iii) increased total antioxidant capacity, glutathione peroxidase and superoxide dismutase in serum (P < 0.05), while decreasing malondialdehyde; (iv) increased serum levels of glucocorticoids, insulin, cortisol and prolactin (P < 0.05), while decreasing the serum levels of triiodothyronine and thyroxine (P < 0.05). In conclusion, under the current experimental conditions, the addition of SC can reduce rectal temperature and respiratory rate in heat-stressed mid-lactation cows, reduce the number of somatic cells in milk and improve the mid-lactation cow performance. In addition, SC addition to the diet can raise serum urea levels, regulate serum hormone levels, boost antioxidant capacity in mid-lactation cows, and boost overall immunity.
Portuguese European Multidisciplinary Seafloor and Water Column Observatory Initiative

The Atlantic dimension of Portugal, with c. 1,700,000 km2 maritime area, led to the prioritization of the European Multidisciplinary Seafloor and water column Observatory - Portugal (EMSO-PT) in the national scientific infrastructures’ roadmap. In this work we present the EMSO-PT initiative: a research consortium joining 15 research institutions, with the aim of implementing a network of multidisciplinary underwater observatories in the Atlantic, as well as laboratories and data processing support infrastructures. EMSO-PT’s priority is to generate continuous scientific data on marine environmental processes related to the interaction between the geosphere, biosphere, and hydrosphere, and to develop new sensors and platforms which will extend ocean monitoring in the near future. Monitoring variables will include biotic and abiotic variables of the ocean floor and water column, namely temperature, salinity, turbidity, acoustics, currents, and dissolved oxygen. Data will be disseminated through European Multidisciplinary Seafloor and Water Column Observatory – European Research Infrastructure Consortiums (EMSO-ERIC) channels, allowing for the integration and open access of data acquired by all partners of EMSO-ERIC, and by the research community at large.
Chromosome-Scale Assembly of the Dendrobium nobile Genome Provides Insights Into the Molecular Mechanism of the Biosynthesis of the Medicinal Active Ingredient of Dendrobium

Orchids constitute approximately 10% of flowering plant species. However, only about 10 orchid genomes have been published. Metabolites are the main way through which orchids respond to their environment. Dendrobium nobile, belonging to Dendrobium, the second largest genus in Orchidaceae, has high ornamental, medicinal, and ecological value. D. nobile is the source of many popular horticultural varieties. Among the Dendrobium species, D. nobile has the highest amount of dendrobine, which is regarded as one of the criteria for evaluating medicinal quality. Due to lack of data and analysis at the genomic level, the biosynthesis pathways of dendrobine and other related medicinal ingredients in D. nobile are unknown. In this paper, we report a chromosome-scale reference genome of D. nobile to facilitate the investigation of its genomic characteristics for comparison with other Dendrobium species. The assembled genome size of D. nobile was 1.19 Gb. Of the sequences, 99.45% were anchored to 19 chromosomes. Furthermore, we identified differences in gene number and gene expression patterns compared with two other Dendrobium species by integrating whole-genome sequencing and transcriptomic analysis [e.g., genes in the polysaccharide biosynthesis pathway and upstream of the alkaloid (dendrobine) biosynthesis pathway]. Differences in the TPS and CYP450 gene families were also found among orchid species. All the above differences might contribute to the species-specific medicinal ingredient biosynthesis pathways. The metabolic pathway-related analysis will provide further insight into orchid responses to the environment. Additionally, the reference genome will provide important insights for further molecular elucidation of the medicinal active ingredients of Dendrobium and enhance the understanding of orchid evolution.
Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2

Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs). We found that miR-483-5p was highly expressed in MM-MSCs, which may be transported through exosomes from MM-MSCs to MM cells to increase miR-483-5p expression in them. We then investigated the role and mechanism of miR-483-5p in the aggressive progression of MM in vitro. We verified that miR-483-5p promoted MM cell proliferation and reduced apoptosis. Then we predicted and validated that TIMP2, a tumor suppressor gene, is the downstream target of miR-483-5p in MM. In summary, our study indicated that MM-MSCs promote MM malignant progression via the release of exosomes and regulation of miR-483-5p/TIMP2 axis, suggesting an essential role of BMSCs derived exosomal miRNA in MM and a potential marker for MM diagnosis and therapy.
Lipidomic Analysis Reveals the Protection Mechanism of GLP-1 Analogue Dulaglutide on High-Fat Diet-Induced Chronic Kidney Disease in Mice

Many clinical studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have renoprotective properties by ameliorating albuminuria and increasing glomerular filtration rate in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) by lowering ectopic lipid accumulation in the kidney. However, the mechanism of GLP-1RAs was hitherto unknown. Here, we conducted an unbiased lipidomic analysis using ultra-high-performance liquid chromatography/electrospray ionization-quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to reveal the changes of lipid composition and distribution in the kidneys of high-fat diet-fed mice after treatment with a long-acting GLP-1RA dulaglutide for 4 weeks. Treatment of dulaglutide dramatically improved hyperglycemia and albuminuria, but there was no substantial improvement in dyslipidemia and ectopic lipid accumulation in the kidney as compared with controls. Intriguingly, treatment of dulaglutide increases the level of an essential phospholipid constituent of inner mitochondrial membrane cardiolipin at the cortex region of the kidneys by inducing the expression of key cardiolipin biosynthesis enzymes. Previous studies demonstrated that lowered renal cardiolipin level impairs kidney function via mitochondrial damage. Our untargeted lipidomic analysis presents evidence for a new mechanism of how GLP-1RAs stimulate mitochondrial bioenergetics via increasing cardiolipin level and provides new insights into the therapeutic potential of GLP-1RAs in mitochondrial-related diseases.