Video-to-music generation demands both a temporally localized high-quality listening experience and globally aligned video-acoustic signatures. While recent music generation models excel at the ...former through advanced audio codecs, the exploration of video-acoustic signatures has been confined to specific visual scenarios. In contrast, our research confronts the challenge of learning globally aligned signatures between video and music directly from paired music and videos, without explicitly modeling domain-specific rhythmic or semantic relationships. We propose V2Meow, a video-to-music generation system capable of producing high-quality music audio for a diverse range of video input types using a multi-stage autoregressive model. Trained on 5k hours of music audio clips paired with video frames mined from in-the-wild music videos, V2Meow is competitive with previous domain-specific models when evaluated in a zero-shot manner. It synthesizes high-fidelity music audio waveforms solely by conditioning on pre-trained general-purpose visual features extracted from video frames, with optional style control via text prompts. Through both qualitative and quantitative evaluations, we demonstrate that our model outperforms various existing music generation systems in terms of visual-audio correspondence and audio quality. Music samples are available at tinyurl.com/v2meow.
MusicLM: Generating Music From Text Agostinelli, Andrea; Denk, Timo I; Borsos, Zalán ...
arXiv (Cornell University),
01/2023
Paper, Journal Article
Odprti dostop
We introduce MusicLM, a model generating high-fidelity music from text descriptions such as "a calming violin melody backed by a distorted guitar riff". MusicLM casts the process of conditional music ...generation as a hierarchical sequence-to-sequence modeling task, and it generates music at 24 kHz that remains consistent over several minutes. Our experiments show that MusicLM outperforms previous systems both in audio quality and adherence to the text description. Moreover, we demonstrate that MusicLM can be conditioned on both text and a melody in that it can transform whistled and hummed melodies according to the style described in a text caption. To support future research, we publicly release MusicCaps, a dataset composed of 5.5k music-text pairs, with rich text descriptions provided by human experts.
We introduce Noise2Music, where a series of diffusion models is trained to generate high-quality 30-second music clips from text prompts. Two types of diffusion models, a generator model, which ...generates an intermediate representation conditioned on text, and a cascader model, which generates high-fidelity audio conditioned on the intermediate representation and possibly the text, are trained and utilized in succession to generate high-fidelity music. We explore two options for the intermediate representation, one using a spectrogram and the other using audio with lower fidelity. We find that the generated audio is not only able to faithfully reflect key elements of the text prompt such as genre, tempo, instruments, mood, and era, but goes beyond to ground fine-grained semantics of the prompt. Pretrained large language models play a key role in this story -- they are used to generate paired text for the audio of the training set and to extract embeddings of the text prompts ingested by the diffusion models. Generated examples: https://google-research.github.io/noise2music
Translation of aberrant mRNAs induces ribosomal collisions, thereby triggering pathways for mRNA and nascent peptide degradation and ribosomal rescue. Here we use sucrose gradient fractionation ...combined with quantitative proteomics to systematically identify proteins associated with collided ribosomes. This approach identified Endothelial differentiation-related factor 1 (EDF1) as a novel protein recruited to collided ribosomes during translational distress. Cryo-electron microscopic analyses of EDF1 and its yeast homolog Mbf1 revealed a conserved 40S ribosomal subunit binding site at the mRNA entry channel near the collision interface. EDF1 recruits the translational repressors GIGYF2 and EIF4E2 to collided ribosomes to initiate a negative-feedback loop that prevents new ribosomes from translating defective mRNAs. Further, EDF1 regulates an immediate-early transcriptional response to ribosomal collisions. Our results uncover mechanisms through which EDF1 coordinates multiple responses of the ribosome-mediated quality control pathway and provide novel insights into the intersection of ribosome-mediated quality control with global transcriptional regulation.
Synaptic degeneration is a major hallmark of Alzheimer’s disease (AD) and the best pathological correlate of cognitive dysfunction. Synaptic markers are therefore a highly desired read-out for ...patient diagnosis and possible follow-up in clinical trials. Several synaptic markers for AD are described in cerebrospinal fluid (CSF), but studies in blood have failed so far. Using quantitative mass spectrometry (IP-MS, MRM) we observed increased concentrations of the presynaptic protein beta-synuclein (βSyn) in CSF and blood of AD patients (n = 64, p < 0.01) and confirmed this finding in two validation cohorts (AD: n = 40 and n = 49, controls: n = 44 and n = 25). βSyn was already increased in patients with mild cognitive impairment (p < 0.01) and was also markedly increased in Creutzfeldt–Jakob disease (CJD; n = 25, p < 0.001) but not behavioral variant frontotemporal dementia (n = 16), dementia with Lewy bodies/Parkinson’s disease dementia (n = 13), Parkinson’s disease (n = 25), or amyotrophic lateral sclerosis (n = 30). The diagnostic sensitivity and specificity for CJD versus other neurodegenerative diseases was ≥96%. These findings suggest βSyn as a candidate blood marker for synaptic degeneration that might be used in clinical AD trials and patient follow-up as part of the recently suggested ATN biomarker panel. It can also serve in the differential diagnosis of CJD.
► We demonstrate substantial antiapoptotic effects of TβMCA on hepatocyte apoptosis. ► TβMCA prevents bile acid-induced breakdown of the mitochondrial membrane potential (MMP). ► TβMCA also restores ...the MMP when the free fatty acid palmitate is used as a hepatotoxin.
β-Muricholic acid (βMCA) is a trihydroxylated bile acid that constitutes the major bile acid in rat and mouse. βMCA is more hydrophilic than ursodeoxycholic acid and has been evaluated for dissolution of cholesterol gallstones. Since it is unknown if βMCA has beneficial effects on hepatocyte cell death we determined the effect of tauro-βMCA (TβMCA) on apoptosis in vitro.
Human Ntcp-transfected HepG2 cells and primary hepatocytes from rat and mouse were incubated with the proapoptotic glycochenodeoxycholic acid (GCDCA) as well as the free fatty acid palmitate in the absence and presence of TβMCA. Apoptosis was quantified using caspase 3/7-assays and after Hoechst 33342 staining. The mitochondrial membrane potential (MMP) was measured fluorometrically using JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-benzimidazol-carbocyaniniodide). Immunoblotting was performed against the proapoptotic Bcl-2-protein Bax.
In Ntcp-HepG2 cells, GCDCA markedly increased apoptosis after 4h. Co-incubation with TβMCA reduced apoptosis to 49% (p<0.01 vs. GCDCA, each; n=6). While GCDCA (100μmol/L) reduced the MMP to 34% after 6h, combination treatment with TβMCA restored the MMP to control levels at all time points (n=4). TβMCA also restored breakdown of the MMP induced by palmitate. GCDCA induced a translocation of Bax from the cytosol to mitochondria that was inhibited by simultaneous treatment with TβMCA in eqimolar concentrations.
TβMCA restricts hepatocellular apoptosis induced by low micromolar concentrations of GCDCA or palmitate via inhibition of Bax translocation to mitochondria and preservation of the MMP. Thus, further studies are warranted to evaluate a potential use of TβMCA in ameliorating liver injury in cholestasis.
Abstract
Background
Synaptic degeneration is a major hallmark of Alzheimer's disease (AD) and the best pathological correlate of cognitive dysfunction. Synaptic markers are therefore a highly desired ...read‐out for patient diagnosis and possible follow‐up in clinical trials in the mainly unsuccessful AD drug development. Several synaptic markers for AD are described in cerebrospinal fluid (CSF) but studies in blood were not successful so far.
Method
We used quantitative mass spectrometry (IP‐MS, MRM) to measure the presynaptic protein beta‐synuclein in CSF and blood from 363 patients: AD (n=64), Creutzfeldt‐Jakob disease (CJD, n=25), behavioural variant frontotemporal dementia (bvFTD, n=16), dementia with Lewy bodies/Parkinson´s disease dementia, (DLB/PDD, n=13), Parkinson´s disease (PD, n=25), amyotrophic lateral sclerosis (ALS, n=30) and non‐neurodegenerative controls (Con, n=45). Changes in AD were validated in two independent validation cohorts from other clinical centers (AD: n=40 and n=49, Con: n=44 and n=25). Group differences were compared by non‐parametric tests and data correlated with clinical scores (MMSE, CDR).
Result
We observed increased concentrations of beta‐synuclein in CSF and blood of AD patients (CSF: median 979pg/mL, IQR: 738‐1223pg/mL vs. 659pg/mL, IQR: 521‐860pg/mL in controls; Serum: 12.9pg/mL, IQR: 10.6‐16.4pg/mL vs. 8.9pg/mL, IQR: 7.1‐10.4pg/mL in controls, p<0.01) and confirmed this finding in the two validation cohorts. Beta‐synuclein was already increased in patients with mild cognitive impairment due to AD (p<0.01). CSF and serum beta‐synuclein was also markedly increased in CJD (CSF: 19324pg/mL, IQR: 10560‐42570pg/mL; Serum: 479pg/mL, IQR: 259‐843pg/mL, p<0.001) but not bvFTD, DLB/PDD, PD or ALS. The diagnostic sensitivity and specificity for CJD versus other neurodegenerative diseases was ³96%.
Conclusion
These findings suggest beta‐synuclein as a candidate blood marker for synaptic degeneration which might be used in clinical AD trials and patient follow‐up as part of the recently suggested ATN biomarker panel. It can also serve in the differential diagnosis of CJD.
Background
Synaptic degeneration is a major hallmark of Alzheimer's disease (AD) and the best pathological correlate of cognitive dysfunction. Synaptic markers are therefore a highly desired read‐out ...for patient diagnosis and possible follow‐up in clinical trials in the mainly unsuccessful AD drug development. Several synaptic markers for AD are described in cerebrospinal fluid (CSF) but studies in blood were not successful so far.
Method
We used quantitative mass spectrometry (IP‐MS, MRM) to measure the presynaptic protein beta‐synuclein in CSF and blood from 363 patients: AD (n=64), Creutzfeldt‐Jakob disease (CJD, n=25), behavioural variant frontotemporal dementia (bvFTD, n=16), dementia with Lewy bodies/Parkinson´s disease dementia, (DLB/PDD, n=13), Parkinson´s disease (PD, n=25), amyotrophic lateral sclerosis (ALS, n=30) and non‐neurodegenerative controls (Con, n=45). Changes in AD were validated in two independent validation cohorts from other clinical centers (AD: n=40 and n=49, Con: n=44 and n=25). Group differences were compared by non‐parametric tests and data correlated with clinical scores (MMSE, CDR).
Result
We observed increased concentrations of beta‐synuclein in CSF and blood of AD patients (CSF: median 979pg/mL, IQR: 738‐1223pg/mL vs. 659pg/mL, IQR: 521‐860pg/mL in controls; Serum: 12.9pg/mL, IQR: 10.6‐16.4pg/mL vs. 8.9pg/mL, IQR: 7.1‐10.4pg/mL in controls, p<0.01) and confirmed this finding in the two validation cohorts. Beta‐synuclein was already increased in patients with mild cognitive impairment due to AD (p<0.01). CSF and serum beta‐synuclein was also markedly increased in CJD (CSF: 19324pg/mL, IQR: 10560‐42570pg/mL; Serum: 479pg/mL, IQR: 259‐843pg/mL, p<0.001) but not bvFTD, DLB/PDD, PD or ALS. The diagnostic sensitivity and specificity for CJD versus other neurodegenerative diseases was ³96%.
Conclusion
These findings suggest beta‐synuclein as a candidate blood marker for synaptic degeneration which might be used in clinical AD trials and patient follow‐up as part of the recently suggested ATN biomarker panel. It can also serve in the differential diagnosis of CJD.
Background & Aims
Hydrophobic bile salts such as glycochenodeoxycholate (GCDC) accumulate in cholestatic liver disease and induce hepatocellular apoptosis, promoting profibrotic signalling. The ...tissue microenvironment is an integral player in cellular pathophysiology, but it is not routinely incorporated into laboratory studies. Tissue oxygen partial pressure (pO2) may be an underestimated component of the microenvironment: in the liver, a pO2 of 30–45 mmHg (approximately 6% O2) is physiological, because of predominant portal blood supply. It was the aim of this project to investigate the impact of physiological hypoxia (i.e. 6% O2) on hepatocellular function, namely, bile salt‐induced apoptosis.
Methods
Human hepatoma cells (HepG2‐Ntcp) and primary rat hepatocytes were cultured at standard laboratory (hyperoxic) conditions (21% O2) and at physiological hypoxia (6% O2) in parallel for 1–8 days to study hepatocellular apoptosis and activation of signalling pathways. Standard laboratory analyses were applied for bile salt uptake, caspase‐3/‐7 activity, western blotting and gene‐array analysis.
Results
Culturing at physiological hypoxia protected both human and rat hepatocytes against GCDC‐induced apoptosis: caspase‐3/‐7 activation was diminished by 3.1 ± 0.5‐fold in human HepG2‐Ntcp and completely abolished in primary rat hepatocytes. Bile salt uptake was unaffected. Induction of hypoxia‐inducible factor‐1α indicated adaption to physiological hypoxia. The MEK/ERK cascade was activated and anti‐apoptotic mediators were induced: N‐Myc down‐regulated gene, gelsolin and carbonic anhydrase IX were upregulated 12.4‐, 6.5‐ and 5.2‐fold respectively.
Conclusions
We conclude from these data that (i) physiological hypoxia protects hepatocytes from bile salt‐induced apoptosis, (ii) tissue pO2 is a crucial, underestimated component of the microenvironment and should (iii) be considered when studying hepatocellular physiology in vitro.
Ursodeoxycholic acid (UDCA) is used in the therapy of cholestatic liver diseases. Apoptosis induced by toxic bile acids plays an important role in the pathogenesis of liver injury during cholestasis ...and appears to be mediated by the human transcription factor AP-1. We aimed to study if TUDCA can decrease taurolitholic acid (TLCA)-induced apoptosis by modulating AP-1. TLCA (20
μM) upregulated AP-1 proteins cFos (26-fold) and JunB (11-fold) as determined by quantitative real-time PCR in HepG2-Ntcp hepatoma cells. AP-1 transcriptional activity increased by 300% after exposure to TLCA. cFos and JunB expression as well as AP-1 transcriptional activity were unaffected by TUDCA (75
μM). However, TUDCA significantly decreased TLCA-induced upregulation of cFos and JunB. Furthermore, TUDCA inhibited TLCA-induced AP-1 transcriptional activity and reduced TLCA-induced apoptosis. These data suggest that reversal of bile acid-induced AP-1 activation may be relevant for the antiapoptotic effect of TUDCA in liver cells.
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