Single-cell transcriptomics and cell-specific proteomics reveals molecular signatures of sleep

Every day, we sleep for a third of the day. Sleep is important for cognition, brain waste clearance, metabolism, and immune responses. The molecular mechanisms governing sleep are largely unknown. Here, we used a combination of single-cell RNA sequencing and cell-type-specific proteomics to interrogate the molecular underpinnings of sleep. Different cell types in three important brain regions for sleep (brainstem, cortex, and hypothalamus) exhibited diverse transcriptional responses to sleep need. Sleep restriction modulates astrocyte-neuron crosstalk and sleep need enhances expression of specific sets of transcription factors in different brain regions. In cortex, we also interrogated the proteome of two major cell types: astrocytes and neurons. Sleep deprivation differentially alters the expression of proteins in astrocytes and neurons. Similarly, phosphoproteomics revealed large shifts in cell-type-specific protein phosphorylation. Our results indicate that sleep need regulates transcriptional, translational, and post-translational responses in a cell-specific manner

Raymond H. Plaut

Free Vibration Analysis of an Inflated Toroidal Shel

Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells.

Circadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms

SlumberNet: deep learning classification of sleep stages using residual neural networks

Abstract Sleep research is fundamental to understanding health and well-being, as proper sleep is essential for maintaining optimal physiological function. Here we present SlumberNet, a novel deep learning model based on residual network (ResNet) architecture, designed to classify sleep states in mice using electroencephalogram (EEG) and electromyogram (EMG) signals. Our model was trained and tested on data from mice undergoing baseline sleep, sleep deprivation, and recovery sleep, enabling it to handle a wide range of sleep conditions. Employing k-fold cross-validation and data augmentation techniques, SlumberNet achieved high levels of overall performance (accuracy = 97%; F1 score = 96%) in predicting sleep stages and showed robust performance even with a small and diverse training dataset. Comparison of SlumberNet's performance to manual sleep stage classification revealed a significant reduction in analysis time (~ 50 × faster), without sacrificing accuracy. Our study showcases the potential of deep learning to facilitate sleep research by providing a more efficient, accurate, and scalable method for sleep stage classification. Our work with SlumberNet further demonstrates the power of deep learning in mouse sleep research

Analysis of differentially expressed genes in leaf rust infected bread wheat involving seedling resistance gene Lr28

Genome-wide transcriptome analysis of seedling resistance to leaf rust conferred by Lr28 gene in wheat (Triticum aestivum L.) was conducted to identify differentially expressed genes during incompatible interaction. A virulent leaf rust race 77-5 was used for inoculation of resistant (HD2329 + Lr28) and susceptible (HD2329 - Lr28) wheat NILs and cDNA-AFLP analyses was carried out. As many as 223 differential transcripts appeared following leaf rust inoculation; these included 122 transcripts that appeared exclusively in resistant NIL, whereas 39 transcripts appeared both in resistant and susceptible NILs. Sequence analyses of 37 transcripts, which appeared in the resistant NIL revealed that 15 transcripts had homology with genes involved in protein synthesis, signal transduction, transport, disease resistance and metabolism. The functions of remaining 22 transcripts could not be determined; these included six novel genes reported for the first time in wheat. Specific primers could be designed for 18 of the 37 transcripts, which included genes with putative and unknown functions. Quantitative real time PCR analysis was conducted using these 18 pairs of primers. A majority (13) of these transcripts appeared within 48 h reaching a peak value at 96 h in resistant NIL signifying their role in providing leaf rust resistance

Copper-Catalyzed Tandem Synthesis of Indolo‑, Pyrrolo[2,1‑<i>a</i>]isoquinolines, Naphthyridines and Bisindolo/Pyrrolo[2,1‑<i>a</i>]isoquinolines via Hydroamination of <i>ortho</i>-Haloarylalkynes Followed by C‑2 Arylation

An efficient approach for the copper-catalyzed regioselective tandem synthesis of diversely substituted indolo­[2,1-<i>a</i>]­isoquinolines <b>11a</b>–<b>r</b>, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>12a</b>–<b>d</b>, and indolo-, pyrrolo­[2,1-<i>f</i>]­[1,6]­naphthyridines <b>14a</b>–<b>f</b> via preferential addition of the heterocyclic amines onto the <i>ortho</i>-haloarylalkynes over <i>N</i>-arylation followed by intramolecular C-2 arylation is described. The scope of the developed chemistry was successfully extended for the direct synthesis of bisindolo-, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>15a</b>–<b>g</b>, a regioisomer of the bisindolo­[1,2-<i>a</i>]­quinolines used as organic single-crystal field-effect transistor. Hydroxymethyl benzotriazole, which is an inexpensive and air stable compound, has been used as a ligand to carry out this one-step conversion of simple, readily available starting materials into an interesting class of heterocyclic compounds

Copper-Catalyzed Tandem Synthesis of Indolo‑, Pyrrolo[2,1‑<i>a</i>]isoquinolines, Naphthyridines and Bisindolo/Pyrrolo[2,1‑<i>a</i>]isoquinolines via Hydroamination of <i>ortho</i>-Haloarylalkynes Followed by C‑2 Arylation

An efficient approach for the copper-catalyzed regioselective tandem synthesis of diversely substituted indolo­[2,1-<i>a</i>]­isoquinolines <b>11a</b>–<b>r</b>, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>12a</b>–<b>d</b>, and indolo-, pyrrolo­[2,1-<i>f</i>]­[1,6]­naphthyridines <b>14a</b>–<b>f</b> via preferential addition of the heterocyclic amines onto the <i>ortho</i>-haloarylalkynes over <i>N</i>-arylation followed by intramolecular C-2 arylation is described. The scope of the developed chemistry was successfully extended for the direct synthesis of bisindolo-, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>15a</b>–<b>g</b>, a regioisomer of the bisindolo­[1,2-<i>a</i>]­quinolines used as organic single-crystal field-effect transistor. Hydroxymethyl benzotriazole, which is an inexpensive and air stable compound, has been used as a ligand to carry out this one-step conversion of simple, readily available starting materials into an interesting class of heterocyclic compounds

Copper-Catalyzed Tandem Synthesis of Indolo‑, Pyrrolo[2,1‑<i>a</i>]isoquinolines, Naphthyridines and Bisindolo/Pyrrolo[2,1‑<i>a</i>]isoquinolines via Hydroamination of <i>ortho</i>-Haloarylalkynes Followed by C‑2 Arylation

An efficient approach for the copper-catalyzed regioselective tandem synthesis of diversely substituted indolo­[2,1-<i>a</i>]­isoquinolines <b>11a</b>–<b>r</b>, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>12a</b>–<b>d</b>, and indolo-, pyrrolo­[2,1-<i>f</i>]­[1,6]­naphthyridines <b>14a</b>–<b>f</b> via preferential addition of the heterocyclic amines onto the <i>ortho</i>-haloarylalkynes over <i>N</i>-arylation followed by intramolecular C-2 arylation is described. The scope of the developed chemistry was successfully extended for the direct synthesis of bisindolo-, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>15a</b>–<b>g</b>, a regioisomer of the bisindolo­[1,2-<i>a</i>]­quinolines used as organic single-crystal field-effect transistor. Hydroxymethyl benzotriazole, which is an inexpensive and air stable compound, has been used as a ligand to carry out this one-step conversion of simple, readily available starting materials into an interesting class of heterocyclic compounds

Palladium-Catalyzed Regioselective [3 + 2] Annulation of Internal Alkynes and Iodo-pyranoquinolines with Concomitant Ring Opening

A regioselective tandem synthesis of highly functionalized pyrrolo[1,2-<i>a</i>]quinolines has been developed through a novel strategy by palladium-catalyzed [3 + 2] annulation of iodo-pyranoquinolines and internal alkynes with subsequent ring opening. Pyranoquinoline with <i>n</i>-alkyl substitution at the 3-position leads to the formation of pyrrolo-acridones <i>via</i> [3 + 2] annulations/ring opening and successive intramolecular cross-aldol condensation