1,721,048 research outputs found
Recommended from our members
Sexual dimorphism in the response to time-restricted feeding and the effects of estrous cycle on female transcriptomics
Get PDFTime-restricted feeding (TRF) is a dietary intervention that limits food intake within 8-10 hours of the active phase. For mice, it has been shown to protect from metabolic disease, as well as reduce damage and inflammation in the context of chronic illnesses. The alignment of feeding with underlying circadian rhythms optimizes the time for when tissues are metabolically active versus undergoing repair and maintenance. Using sequencing and mass spectrometry, we have curated a unique timeseries dataset of male and female mice fed a Western high-fat diet undergoing TRF. Physiologically, male and female mice responded similarly to TRF by reducing hepatic lipid storage and improve glucose tolerance, however females were not protected from gaining fat mass. Improvements to motor coordination was only observed in male mice as well. Moreover, organizing a multi- tissue and multi- omics response to TRF has highlighted that males respond more than females to temporal restrictions in feeding but the curious effect of increasing rhythmicity is observed in both sexes. Furthermore, the question of hormonal differences in females due to the estrous cycle presents another avenue to be explored, as estrogen has been implicated in protections from metabolic diseases as well. To do so, we examined differences in female transcriptome across the peak (proestrus) and trough (metestrus) of the estrous cycle. Not surprisingly, reproductive tissues such as the uterus respond more greatly than metabolic tissues like the liver to different stages of the hormonal profiles. However, the liver does seem to prioritize certain metabolic states according to the stage of the estrous cycle. Utilizing high-fat diet as a challenge, we observe that diet induces transcriptomic differences at specific stages of the estrous cycle, resulting in chronic disruption of estrous- regulated processes and eventual disruption of the reproductive cycle. In applying TRF, females on high- fat diet were observed to reduce the amount of time spent in low- estrogen states and complete more cycles in a fixed period compared to their ad lib counterparts. Overall, our results suggest that TRF is beneficial life-style intervention for both sexes and estrous cycle consideration depends on experimental design
Recommended from our members
Analysis of the Projections of Melanopsin Expressing Retinal Ganglion Cells to the SCN
Get PDFThe suprachiasmatic nucleus (SCN) of the hypothalamus is known as the master clock, which controls mammalian circadian rhythms. Located in the brain above the optic chiasm, the SCN entrains to daily environmental light cycles via innervations from the retina. Intrinsically photosensitive retinal ganglion cells (mRGCs), which express the photopigment melanopsin, send axonal projections down the retinohypothalamic tract (RHT). Each mRGC communicates with neurons in the SCN via boutons, small swellings along its axonal length filled with vesicles containing neuropeptides. The SCN consists of two morphologically distinct regions where synaptic connections of the RHT deliver light information: the core and the shell. In this study we reconstructed the connectome of the mRGC network in the shell and core regions of the SCN using the electron microscopy tag APEX2, and characterized differences in the structures of the two SCN regions using IMOD software to reconstruct 3D images of neurons. Quantification of synaptic strength between mRGCs and the SCN was evaluated by measuring the bouton density and average volume of mRGC synapses. We found that the average bouton volume of the mRGC contacts in the SCN shell are significantly larger than those in the SCN core however, mRGCs make fewer connections in the shell than the core. Reconstruction of the neuronal connections is necessary for the understanding of the flow of information from the retina to the SCN, and this understanding may aid and expedite the development of therapies targeting disruptions in the mammalian circadian rhythms
Recommended from our members
Ultrastructure of Melanopsin-Expressing Retinal Ganglion Cell Circuitry in the Retina and Brain Regions that Mediate Light-Driven Behavior
Get PDFMelanopsin-expressing retinal ganglion cells (mRGC) are intrinsically photosensitive and combine their melanopsin-based photoresponses with rod and cone signals to convey light information to a subset of retinal brain targets. mRGC axons to non-image forming (NIF) visual centers are essential for the proper functioning of processes like circadian photoentrainment and pupillary light reflex. Surprisingly, mRGCs also send axons to image-forming regions of the brain. It is unknown how mRGCs mediate such diverse functions. Classically, a cell’s morphology and location in a biological system is a direct reflection of its synaptic connections and, by definition, their function. mRGCs can be divided into five subtypes (M1-M5) based on morphology and dendritic stratification in the inner plexiform layer. In the classical sense, since M1s send axons to only a subset of mRGC-target regions and are the only subtype that monostratify in the OFF-sublamina, M1s likely serve a distinct function from other subtypes. However, M1s, like all mRGCs, exhibit an ON-response. This reveals a hole in what we understand about intraretinal connectivity and attenuates the weight that should be afforded to stratification in determining function. While the other mRGC subtypes have distinct morphology and branching patterns, it is unknown whether they serve specific functions. Thus, in order to explore the structure-function relationship of mRGC subtypes, we must consider connectivity. Unfortunately, the variable expression of melanopsin protein between subtypes and across the architecture of a single mRGC and the lack of unique markers for up- and downstream interactors has precluded rigorous study of mRGC connectivity in the retina and central targets.We use a correlated light and electron microscopy label and serial blockface scanning electron microscopy to explore the architecture and synaptic partners of mRGCs in an attempt to better understand the connectivity of mRGC subtypes. We show significant differences in the ultrastructure of mRGC axonal terminals in mRGC-recipient brain regions, stratification-specific differences in mRGC dendrites, and catalog the intraretinal connections specific to mRGC subtypes
Recommended from our members
Time Restricted Feeding on Age-Related Physiological Decline and Skeletal Muscle Function
Get PDFAging is a natural part of an organism’s life cycle. It is, however, associated with increased risks for many chronic diseases including obesity and sarcopenia. Aging is also associated with dampened functions of the circadian clock, an internal timing system that orchestrates physiological function and behavior and displays recurrent daily 24h rhythms. The circadian clock has an intricate relationship with metabolic regulators and plays a key role in the daily partitioning of energy producing/consuming processes for the efficient functioning of metabolism. Time-restricted feeding (TRF) – a feeding regime that restricts caloric intake to an 8-9 hour feeding window in the active phase of an organism – is conceptualized as a method of synchronizing feeding-fasting cycles with endogenous circadian clock. TRF is a particularly innovative dieting strategy because it does not require alterations in caloric quantity/quality, thus rendering TRF an easy to adopt and yet highly efficacious intervention. The ability of TRF to holistically improve numerous health parameters in young mice makes it an attractive candidate for the prevention (or delay) of sarcopenia and age-related metabolic decline. Here we showed that TRF prevents body weight gain, reduces fat mass, preserves lean mass, bolsters glucose regulation, improves endurance and strength, and enhances muscle clock gene expression, all without caloric restriction and irrespective of age in male C57BL/6J mice fed a western diet. Thus, TRF can delay age-related physiological decline in middle-aged mice and our results set stage for further exploration of the benefits of TRF across lifespan
Recommended from our members
Classification of NREM Heterogeneity with Machine Learning Approach Reveals Distinct Temporal and Functional Pattern of NREM Sleep
Get PDFSleep is a phenomenon that impacts substantial hours of people in 24 hours. Cortical activity is distinct during different phases of sleep. In fact, the gold standard for sleep measurement is polysomnogram (PSG) consisting of electroencephalography (EEG), electromyography (EMG), and electrooculography (EOG). The combination of brainwave activity, muscular activity, and eye movement delineate different stages of sleep in humans. Sleep in small animal models is also possible with EEG/EMG. Classically, sleep is scored by visual examination on the characteristics of the EEG (frequency and amplitude). In mice, sleep is grossly categorized as rapid eye movement (REM) or non-REM (NREM) sleep. REM sleep has unique characteristics for EEG (high frequency, low amplitude, desynchronized waveforms) and EMG (near absent due to muscle atonia). For NREM sleep, the patterns for EEG are highly heterogeneous, making the fine mapping of NREM sleep technically challenging and error-prone among different scorers. NREM sleep is not uniform. The ability to objectively evaluate the subtle stages of NREM sleep allows us to appreciate the function of NREM sleep. My thesis focuses on developing a technique that better characterizes distinct clusters of NREM sleep based on the differential potential of EEG at different frequencies in both normal and disrupted sleep conditions. We proposed that, by mapping NREM sleep to a finer resolution, we will reveal distinct temporal and functional patterns of NREM sleep. We used the machine learning technique, K-mean Clustering, to subcategorized NREM into eight different clusters with distinct EEG patterns. These clusters exhibit temporal specificity at different phases of sleep. Finally, we demonstrated that different NREM clusters are differentially affected by the experimental disruption of sleep. Our method elicits the complexity of NREM sleep, enabling us to investigate whether specific sequences of NREM clusters exist in normal and pathological sleep
Recommended from our members
Understanding Sleep Disruption and Sepsis Survival in Pathogen-free Peritonitis with an Ex Vivo Model
Get PDFSepsis, a leading cause of mortality in hospitalized patients, is deeply impacted by sleep disruption, a common issue in hospital settings. The mechanisms connecting sleep disruption and sepsis outcomes remain elusive. We have demonstrated that sleep-disrupted C57BL/6 mice have a higher survival rate in an endotoxin-mediated peritonitis model. In this study, we test the hypothesis on whether the improved survival was due to impaired cell-intrinsic immune response to endotoxin. Using a tactile model for sleep disruption, we compared the ex vivo lipopolysaccharide (LPS) activation of primary peritoneal immune cells from sleep-disrupted mice to that of normal sleep control. After seven days of sleep disruption, cells from peritoneal lavage were plated and activated with LPS (100ng/mL) for 3 hours. We assessed inflammatory transcriptional activation by quantitative PCR (RT-qPCR) and found no reduction in cytokine genes such as Tnf⍺, Il-1ꞵ, Il-6, and Il-10 in sleep-disrupted mice. Flow cytometry of resident peritoneal macrophages showed that LPS induced STAT1 activation (phosphorylation at serine 727) was not reduced in peritoneal immune cells from sleep-disrupted mice compared to control. Finally, preliminary analysis of IL-1β secretion through ELISA also showed no sign of reduced immune activation after sleep disruption. Our findings suggest that the ex vivo activation of peritoneal immune cells by LPS is not dampened by sleep disruption. The mechanism for increased sepsis survival in sleep-disrupted mice lies outside of the initial contact between peritoneal immune cells and endotoxin, warranting further investigation to understand sleep-immune interactions during sepsis
Chronophotopharmacology:Methodology for High Spatiotemporal Control Over the Circadian Rhythm with Light
No full textInspired by the crucial role of circadian clock disruption in disease development, chemical biology developed small molecule modifiers to adjust cellular clocks. However, the application of these modifiers faces a key challenge: due to the similarity in the cellular regulation of clocks, besides curing the locally disrupted biological rhythm, they would affect all the other, healthy rhythms. To overcome this problem, a potential strategy would be regulation of a compound’s bioactivity with light, which can be delivered precisely in space and time. Here, we describe the methodology of how to design, develop, and apply photo-responsive modulators, based on photocleavable protecting groups and photoswitches, for the local manipulation of the circadian rhythm. Methods presented in this book chapter allow for control of the circadian period in cells, ex vivo and in a living organism, and for the first time enable the modulation of the circadian phase.</p
Multiple Photopigments Entrain the Mammalian Circadian Oscillator
No full textCircadian rhythms are entrained to the natural day:night cycle. Melanopsin expressed in retinal ganglion cells partially accounts for circadian photoentrainment. Dkhissi-Benyahya et al. demonstrate that medium wavelength opsin (MW-opsin) also plays an important role in the process. Furthermore, they develop a model explaining wavelength-dependent photoentrainment by melanopsin and MW-opsin
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
