Cryo-electron microscopy (cryo-EM) single-particle analysis has proven powerful in determining the structures of rigid macromolecules. However, many imaged protein complexes exhibit conformational ...and compositional heterogeneity that poses a major challenge to existing three-dimensional reconstruction methods. Here, we present cryoDRGN, an algorithm that leverages the representation power of deep neural networks to directly reconstruct continuous distributions of 3D density maps and map per-particle heterogeneity of single-particle cryo-EM datasets. Using cryoDRGN, we uncovered residual heterogeneity in high-resolution datasets of the 80S ribosome and the RAG complex, revealed a new structural state of the assembling 50S ribosome, and visualized large-scale continuous motions of a spliceosome complex. CryoDRGN contains interactive tools to visualize a dataset's distribution of per-particle variability, generate density maps for exploratory analysis, extract particle subsets for use with other tools and generate trajectories to visualize molecular motions. CryoDRGN is open-source software freely available at http://cryodrgn.csail.mit.edu .
Health benefits of dietary fiber Anderson, James W; Baird, Pat; Davis, Richard H. Jr ...
Nutrition reviews,
April 2009, Letnik:
67, Številka:
4
Journal Article
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Dietary fiber intake provides many health benefits. However, average fiber intakes for US children and adults are less than half of the recommended levels. Individuals with high intakes of dietary ...fiber appear to be at significantly lower risk for developing coronary heart disease, stroke, hypertension, diabetes, obesity, and certain gastrointestinal diseases. Increasing fiber intake lowers blood pressure and serum cholesterol levels. Increased intake of soluble fiber improves glycemia and insulin sensitivity in non-diabetic and diabetic individuals. Fiber supplementation in obese individuals significantly enhances weight loss. Increased fiber intake benefits a number of gastrointestinal disorders including the following: gastroesophageal reflux disease, duodenal ulcer, diverticulitis, constipation, and hemorrhoids. Prebiotic fibers appear to enhance immune function. Dietary fiber intake provides similar benefits for children as for adults. The recommended dietary fiber intakes for children and adults are 14 g/1000 kcal. More effective communication and consumer education is required to enhance fiber consumption from foods or supplements.
A growing body of evidence shows that ongoing oscillations in auditory cortex modulate their phase to match the rhythm of temporally regular acoustic stimuli, increasing sensitivity to relevant ...environmental cues and improving detection accuracy. In the current study, we test the hypothesis that nonsensory information provided by linguistic content enhances phase-locked responses to intelligible speech in the human brain. Sixteen adults listened to meaningful sentences while we recorded neural activity using magnetoencephalography. Stimuli were processed using a noise-vocoding technique to vary intelligibility while keeping the temporal acoustic envelope consistent. We show that the acoustic envelopes of sentences contain most power between 4 and 7 Hz and that it is in this frequency band that phase locking between neural activity and envelopes is strongest. Bilateral oscillatory neural activity phase-locked to unintelligible speech, but this cerebro-acoustic phase locking was enhanced when speech was intelligible. This enhanced phase locking was left lateralized and localized to left temporal cortex. Together, our results demonstrate that entrainment to connected speech does not only depend on acoustic characteristics, but is also affected by listeners' ability to extract linguistic information. This suggests a biological framework for speech comprehension in which acoustic and linguistic cues reciprocally aid in stimulus prediction.
Due to their periodic nature, neural oscillations might represent an optimal “tool” for the processing of rhythmic stimulus input 1–3. Indeed, the alignment of neural oscillations to a rhythmic ...stimulus, often termed phase entrainment, has been repeatedly demonstrated 4–7. Phase entrainment is central to current theories of speech processing 8–10 and has been associated with successful speech comprehension 11–17. However, typical manipulations that reduce speech intelligibility (e.g., addition of noise and time reversal 11, 12, 14, 16, 17) could destroy critical acoustic cues for entrainment (such as “acoustic edges” 7). Hence, the association between phase entrainment and speech intelligibility might only be “epiphenomenal”; i.e., both decline due to the same manipulation, without any causal link between the two 18. Here, we use transcranial alternating current stimulation (tACS 19) to manipulate the phase lag between neural oscillations and speech rhythm while measuring neural responses to intelligible and unintelligible vocoded stimuli with sparse fMRI. We found that this manipulation significantly modulates the BOLD response to intelligible speech in the superior temporal gyrus, and the strength of BOLD modulation is correlated with a phasic modulation of performance in a behavioral task. Importantly, these findings are absent for unintelligible speech and during sham stimulation; we thus demonstrate that phase entrainment has a specific, causal influence on neural responses to intelligible speech. Our results not only provide an important step toward understanding the neural foundation of human abilities at speech comprehension but also suggest new methods for enhancing speech perception that can be explored in the future.
•Phase lag between neural oscillations and speech rhythm was manipulated using tACS•This manipulation modulated the BOLD response to speech in superior temporal gyrus•tACS effects were observed for intelligible, but not unintelligible, speech•Results show a causal role of neural entrainment during speech processing
Using simultaneous tACS-fMRI recordings, Zoefel et al. show that the alignment of neural oscillations to stimulus rhythm causally modulates neural responses to speech. The effect is specific for intelligible speech, supporting the notion that neural entrainment is a mechanism tailored to optimize speech processing.
A key feature of speech is the quasi-regular rhythmic information contained in its slow amplitude modulations. In this article we review the information conveyed by speech rhythm, and the role of ...ongoing brain oscillations in listeners' processing of this content. Our starting point is the fact that speech is inherently temporal, and that rhythmic information conveyed by the amplitude envelope contains important markers for place and manner of articulation, segmental information, and speech rate. Behavioral studies demonstrate that amplitude envelope information is relied upon by listeners and plays a key role in speech intelligibility. Extending behavioral findings, data from neuroimaging - particularly electroencephalography (EEG) and magnetoencephalography (MEG) - point to phase locking by ongoing cortical oscillations to low-frequency information (~4-8 Hz) in the speech envelope. This phase modulation effectively encodes a prediction of when important events (such as stressed syllables) are likely to occur, and acts to increase sensitivity to these relevant acoustic cues. We suggest a framework through which such neural entrainment to speech rhythm can explain effects of speech rate on word and segment perception (i.e., that the perception of phonemes and words in connected speech is influenced by preceding speech rate). Neuroanatomically, acoustic amplitude modulations are processed largely bilaterally in auditory cortex, with intelligible speech resulting in differential recruitment of left-hemisphere regions. Notable among these is lateral anterior temporal cortex, which we propose functions in a domain-general fashion to support ongoing memory and integration of meaningful input. Together, the reviewed evidence suggests that low-frequency oscillations in the acoustic speech signal form the foundation of a rhythmic hierarchy supporting spoken language, mirrored by phase-locked oscillations in the human brain.
Successful perception depends on combining sensory input with prior knowledge. However, the underlying mechanism by which these two sources of information are combined is unknown. In speech ...perception, as in other domains, two functionally distinct coding schemes have been proposed for how expectations influence representation of sensory evidence. Traditional models suggest that expected features of the speech input are enhanced or sharpened via interactive activation (Sharpened Signals). Conversely, Predictive Coding suggests that expected features are suppressed so that unexpected features of the speech input (Prediction Errors) are processed further. The present work is aimed at distinguishing between these two accounts of how prior knowledge influences speech perception. By combining behavioural, univariate, and multivariate fMRI measures of how sensory detail and prior expectations influence speech perception with computational modelling, we provide evidence in favour of Prediction Error computations. Increased sensory detail and informative expectations have additive behavioural and univariate neural effects because they both improve the accuracy of word report and reduce the BOLD signal in lateral temporal lobe regions. However, sensory detail and informative expectations have interacting effects on speech representations shown by multivariate fMRI in the posterior superior temporal sulcus. When prior knowledge was absent, increased sensory detail enhanced the amount of speech information measured in superior temporal multivoxel patterns, but with informative expectations, increased sensory detail reduced the amount of measured information. Computational simulations of Sharpened Signals and Prediction Errors during speech perception could both explain these behavioural and univariate fMRI observations. However, the multivariate fMRI observations were uniquely simulated by a Prediction Error and not a Sharpened Signal model. The interaction between prior expectation and sensory detail provides evidence for a Predictive Coding account of speech perception. Our work establishes methods that can be used to distinguish representations of Prediction Error and Sharpened Signals in other perceptual domains.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Reading in many alphabetic writing systems depends on both item-specific knowledge used to read irregular words (sew, yacht) and generative spelling-sound knowledge used to read pseudowords (tew, ...yash). Research into the neural basis of these abilities has been directed largely by cognitive accounts proposed by the dual-route cascaded and triangle models of reading. We develop a framework that enables predictions for neural activity to be derived from cognitive models of reading using 2 principles: (a) the extent to which a model component or brain region is engaged by a stimulus and (b) how much effort is exerted in processing that stimulus. To evaluate the derived predictions, we conducted a meta-analysis of 36 neuroimaging studies of reading using the quantitative activation likelihood estimation technique. Reliable clusters of activity are localized during word versus pseudoword and irregular versus regular word reading and demonstrate a great deal of convergence between the functional organization of the reading system put forward by cognitive models and the neural systems activated during reading tasks. Specifically, left-hemisphere activation clusters are revealed reflecting orthographic analysis (occipitotemporal cortex), lexical and/or semantic processing (anterior fusiform, middle temporal gyrus), spelling-sound conversion (inferior parietal cortex), and phonological output resolution (inferior frontal gyrus). Our framework and results establish that cognitive models of reading are relevant for interpreting neuroimaging studies and that neuroscientific studies can provide data relevant for advancing cognitive models. This article thus provides a firm empirical foundation from which to improve integration between cognitive and neural accounts of the reading process.
to evaluate the performance of the 4 'A's Test (4AT) in screening for delirium in older patients. The 4AT is a new test for rapid screening of delirium in routine clinical practice.
: prospective ...study of consecutively admitted elderly patients with independent 4AT and reference standard assessments.
: an acute geriatrics ward and a department of rehabilitation.
two hundred and thirty-six patients (aged ≥70 years) consecutively admitted over a period of 4 months.
in each centre, the 4AT was administered by a geriatrician to eligible patients within 24 h of admission. Reference standard delirium diagnosis (DSM-IV-TR criteria) was obtained within 30 min by a different geriatrician who was blind to the 4AT score. The presence of dementia was assessed using the Alzheimer's Questionnaire and the informant section of the Clinical Dementia Rating scale. The main outcome measure was the accuracy of the 4AT in diagnosing delirium.
patients were 83.9 ± 6.1 years old, and the majority were women (64%). Delirium was detected in 12.3% (n = 29), dementia in 31.2% (n = 74) and a combination of both in 7.2% (n = 17). The 4AT had a sensitivity of 89.7% and specificity 84.1% for delirium. The areas under the receiver operating characteristic curves for delirium diagnosis were 0.93 in the whole population, 0.92 in patients without dementia and 0.89 in patients with dementia.
the 4AT is a sensitive and specific method of screening for delirium in hospitalised older people. Its brevity and simplicity support its use in routine clinical practice.
Bacterial ribosome biogenesis has been an active area of research for more than 30 years and has served as a test-bed for the development of new biochemical, biophysical and structural techniques to ...understand macromolecular assembly generally. Recent work inspecting the process in vivo has advanced our understanding of the role of ribosome biogenesis factors, the co-transcriptional nature of assembly, the kinetics of the process under sub-optimal conditions, and the rRNA folding and ribosome protein binding pathways. Additionally, new structural work enabled by single-particle electron microscopy has helped to connect in vitro ribosomal protein binding maps to the underlying RNA. This review summarizes the state of these in vivo studies, provides a kinetic model for ribosome assembly under sub-optimal conditions, and describes a framework to compare newly emerging assembly intermediate structures.
This article is part of the themed issue ‘Perspectives on the ribosome’.
How humans extract the identity of speech sounds from highly variable acoustic signals remains unclear. Here, we use searchlight representational similarity analysis (RSA) to localize and ...characterize neural representations of syllables at different levels of the hierarchically organized temporo-frontal pathways for speech perception. We asked participants to listen to spoken syllables that differed considerably in their surface acoustic form by changing speaker and degrading surface acoustics using noise-vocoding and sine wave synthesis while we recorded neural responses with functional magnetic resonance imaging. We found evidence for a graded hierarchy of abstraction across the brain. At the peak of the hierarchy, neural representations in somatomotor cortex encoded syllable identity but not surface acoustic form, at the base of the hierarchy, primary auditory cortex showed the reverse. In contrast, bilateral temporal cortex exhibited an intermediate response, encoding both syllable identity and the surface acoustic form of speech. Regions of somatomotor cortex associated with encoding syllable identity in perception were also engaged when producing the same syllables in a separate session. These findings are consistent with a hierarchical account of how variable acoustic signals are transformed into abstract representations of the identity of speech sounds.
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