The hidden world of amyloid biology has suddenly snapped into atomic-level focus, revealing over 80 amyloid protein fibrils, both pathogenic and functional. Unlike globular proteins, amyloid proteins ...flatten and stack into unbranched fibrils. Stranger still, a single protein sequence can adopt wildly different two-dimensional conformations, yielding distinct fibril polymorphs. Thus, an amyloid protein may define distinct diseases depending on its conformation. At the heart of this conformational variability lies structural frustrations. In functional amyloids, evolution tunes frustration levels to achieve either stability or sensitivity according to the fibril’s biological function, accounting for the vast versatility of the amyloid fibril scaffold.
A wealth of recent amyloid structures begins to illuminate these puzzling protein conformations, shedding light on how and why different conformations contribute to cellular function or disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Dielectrophoretic analysis of cell electrical properties via the Clausius–Mossotti model has been widely used to estimate values of the membrane conductance, membrane capacitance and cytoplasm ...conductivity of cells. However, although the latter two values produced by this method compare well to those acquired by other electrophysiological methods, the membrane conductance is often substantially larger than that acquired by methods such as patch clamp. In this paper, the electrical properties of red blood cells (RBC) are analysed at two conductivities and following membrane‐altering treatments, to develop a mathematical model of membrane conductance. Results suggest that the RBC “membrane conductance” term is primarily dominated by surface conduction, comprising an element related to medium conductivity augmented by conduction in the electrical double layer, which is in turn altered by the cell membrane potential. Validation of the relationship between membrane potential and membrane conductance was performed using platelets, where a similar relationship was observed. This sheds new light on the origin and significance of the membrane conductance term and explains for the first time phenomena of alterations in the parameter counter to changes in membrane potential or cytoplasm conductivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all ...protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional "rush hours" preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spiiceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Coastal wetlands are a critical component of the coastal landscape that are increasingly threatened by sea level rise and other human disturbance. Periodically mapping wetland distribution is crucial ...to coastal ecosystem management. Ensemble algorithms (EL), such as random forest (RF) and gradient boosting machine (GBM) algorithms, are now commonly applied in the field of remote sensing. However, the performance and potential of other EL methods, such as extreme gradient boosting (XGBoost) and bagged trees, are rarely compared and tested for coastal wetland mapping. In this study, we applied the three most widely used EL techniques (i.e., bagging, boosting and stacking) to map wetland distribution in a highly modified coastal catchment, the Manning River Estuary, Australia. Our results demonstrated the advantages of using ensemble classifiers to accurately map wetland types in a coastal landscape. Enhanced bagging decision trees, i.e., classifiers with additional methods to increasing ensemble diversity such as RF and weighted subspace random forest, had comparably high predictive power. For the stacking method evaluated in this study, our results are inconclusive, and further comprehensive quantitative study is encouraged. Our findings also suggested that the ensemble methods were less effective at discriminating minority classes in comparison with more common classes. Finally, the variable importance results indicated that hydro-geomorphic factors, such as tidal depth and distance to water edge, were among the most influential variables across the top classifiers. However, vegetation indices derived from longer time series of remote sensing data that arrest the full features of land phenology are likely to improve wetland type separation in coastal areas.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Detecting periodicity in large scale data remains a challenge. While efforts have been made to identify best of breed algorithms, relatively little research has gone into integrating these methods in ...a generalizable method. Here, we present MetaCycle, an R package that incorporates ARSER, JTK_CYCLE and Lomb-Scargle to conveniently evaluate periodicity in time-series data. MetaCycle has two functions, meta2d and meta3d, designed to analyze two-dimensional and three-dimensional time-series datasets, respectively. Meta2d implements N-version programming concepts using a suite of algorithms and integrating their results.
MetaCycle package is available on the CRAN repository (https://cran.r-project.org/web/packages/MetaCycle/index.html) and GitHub (https://github.com/gangwug/MetaCycle).
hogenesch@gmail.comSupplementary information: Supplementary data are available at Bioinformatics online.
Imbalances in amount and timing of sleep are harmful to physical and mental health. Therefore, the study of the underlying mechanisms is of great biological importance. Proper timing and amount of ...sleep are regulated by both the circadian clock and homeostatic sleep drive. However, very little is known about the cellular and molecular mechanisms by which the circadian clock regulates sleep. In this study, we describe a novel role for diuretic hormone 31 (DH31), the fly homolog of the vertebrate neuropeptide calcitonin gene-related peptide, as a circadian wake-promoting signal that awakens the fly in anticipation of dawn.
Analysis of loss-of-function and gain-of-function Drosophila mutants demonstrates that DH31 suppresses sleep late at night. DH31 is expressed by a subset of dorsal circadian clock neurons that also express the receptor for the circadian neuropeptide pigment-dispersing factor (PDF). PDF secreted by the ventral pacemaker subset of circadian clock neurons acts on PDF receptors in the DH31-expressing dorsal clock neurons to increase DH31 secretion before dawn. Activation of PDF receptors in DH31-positive DN1 specifically affects sleep and has no effect on circadian rhythms, thus constituting a dedicated locus for circadian regulation of sleep.
We identified a novel signaling molecule (DH31) as part of a neuropeptide relay mechanism for circadian control of sleep. Our results indicate that outputs of the clock controlling sleep and locomotor rhythms are mediated via distinct neuronal pathways.
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•CGRP is a wake-promoting neuropeptide that regulates sleep maintenance at night•CGRP is expressed by a restricted subset of circadian clock neurons•These neurons are downstream of circadian PDF neuropeptide signals•CGRP is a sleep-specific clock output and does not affect circadian timekeeping
Timing of sleep is important for physical and mental health and is regulated by the circadian clock. Kunst et al. describe neuropeptide CGRP as a novel wake-promoting clock output that regulates sleep in Drosophila melanogaster. CGRP is expressed by a restricted subset of clock neurons, and its release is modulated by the circadian neuropeptide PDF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This biography examines the long life of the traveller and author Stephen Graham. Graham walked across large parts of the Tsarist Empire in the years before 1917, describing his adventures in a ...series of books and articles that helped to shape attitudes towards Russia in Britain and the United States. In later years he travelled widely across Europe and North America, meeting some of the best known writers of the twentieth century, including H.G.Wells and Ernest Hemingway. Graham also wrote numerous novels and biographies that won him a wide readership on both sides of the Atlantic. This book traces Graham’s career as a world traveller, and provides a rich portrait of English, Russian and American literary life in the first half of the twentieth century. It also examines how many aspects of his life and writing coincide with contemporary concerns, including the development of New Age spirituality and the rise of environmental awareness. Beyond Holy Russia is based on extensive research in archives of private papers in Britain and the USA and on the many works of Graham himself. The author describes with admirable tact and clarity Graham’s heterodox and convoluted spiritual quest. The result is a fascinating portrait of a man who was for many years a significant literary figure on both sides of the Atlantic.
The circadian clock is a molecular and cellular oscillator found in most mammalian tissues that regulates rhythmic physiology and behavior. Numerous investigations have addressed the contribution of ...circadian rhythmicity to cellular, organ, and organismal physiology. We recently developed a method to look at transcriptional oscillations with unprecedented precision and accuracy using high-density time sampling. Here, we report a comparison of oscillating transcription from mouse liver, NIH3T3, and U2OS cells. Several surprising observations resulted from this study, including a 100-fold difference in the number of cycling transcripts in autonomous cellular models of the oscillator versus tissues harvested from intact mice. Strikingly, we found two clusters of genes that cycle at the second and third harmonic of circadian rhythmicity in liver, but not cultured cells. Validation experiments show that 12-hour oscillatory transcripts occur in several other peripheral tissues as well including heart, kidney, and lungs. These harmonics are lost ex vivo, as well as under restricted feeding conditions. Taken in sum, these studies illustrate the importance of time sampling with respect to multiple testing, suggest caution in use of autonomous cellular models to study clock output, and demonstrate the existence of harmonics of circadian gene expression in the mouse.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Digital Technology for Diabetes Hughes, Michael S; Addala, Ananta; Buckingham, Bruce
The New England journal of medicine,
2023-Nov-30, 2023-11-30, 20231130, Volume:
389, Issue:
22
Journal Article
Peer reviewed
Digital Technology for DiabetesMonitors to measure glucose levels have been paired with software controlling insulin delivery. The authors examine the state of the art in digital technology to manage ...diabetes (types 1 and 2).
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