12-h clock regulation of genetic information flow by XBP1s

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pan, Y., Ballance, H., Meng, H., Gonzalez, N., Kim, S., Abdurehman, L., York, B., Chen, X., Schnytzer, Y., Levy, O., Dacso, C. C., McClung, C. A., O'Malley, B. W., Liu, S., & Zhu, B. 12-h clock regulation of genetic information flow by XBP1s. Plos Biology, 18(1), (2020): e3000580, doi:10.1371/journal.pbio.3000580.Our group recently characterized a cell-autonomous mammalian 12-h clock independent from the circadian clock, but its function and mechanism of regulation remain poorly understood. Here, we show that in mouse liver, transcriptional regulation significantly contributes to the establishment of 12-h rhythms of mRNA expression in a manner dependent on Spliced Form of X-box Binding Protein 1 (XBP1s). Mechanistically, the motif stringency of XBP1s promoter binding sites dictates XBP1s’s ability to drive 12-h rhythms of nascent mRNA transcription at dawn and dusk, which are enriched for basal transcription regulation, mRNA processing and export, ribosome biogenesis, translation initiation, and protein processing/sorting in the Endoplasmic Reticulum (ER)-Golgi in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). We further identified GA-binding proteins (GABPs) as putative novel transcriptional regulators driving 12-h rhythms of gene expression with more diverse phases. These 12-h rhythms of gene expression are cell autonomous and evolutionarily conserved in marine animals possessing a circatidal clock. Our results demonstrate an evolutionarily conserved, intricate network of transcriptional control of the mammalian 12-h clock that mediates diverse biological pathways. We speculate that the 12-h clock is coopted to accommodate elevated gene expression and processing in mammals at the two rush hours, with the particular genes processed at each rush hour regulated by the circadian and/or tissue-specific pathways.This study was supported by the American Diabetes Association junior faculty development award 1-18-JDF-025 to B.Z., by funding from National Institute of Health HD07879 and 1P01DK113954 to B.W.O, by funding from National Science Foundation award 1703170 to C.C.D. and B.Z., and by funding from Brockman Foundation to C.C.D and B.W.O. This work was further supported by the UPMC Genome Center with funding from UPMC’s Immunotherapy and Transplant Center. This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. Research reported in this publication was further supported by the National Institute of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under award number P30DK120531 to Pittsburgh Liver Research Center, in which both S.L. and B.Z. are members. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Sm-CeO₂/Zeolite Bifunctional Catalyst for Direct and Highly Selective Conversion of Bioethanol to Propylene

A series of Sm-CeO2/Beta composites with various Beta contents were prepared by an incipient impregnation method, followed by calcination at 650 °C. They were characterized by XRD, N2 adsorption, SEM, NH3-TPD, CO2-TPD and 27Al MAS NMR. The Sm-CeO2/Beta bifunctional catalysts exhibit eminent catalytic performances in the selective conversion of ethanol to propylene. In particular, the Sm-CeO2/10%Beta catalyst with 10% Beta zeolite gives the highest C3H6 yield of 59.3%. A good match between Sm-CeO2 and Beta accounts for its optimal result

MoSe2 nanoflakes-decorated vertically aligned carbon nanotube film on nickel foam as a binder-free supercapacitor electrode with high rate capability

International audienc

The relationship between disrupted anhedonia-related circuitry and suicidal ideation in major depressive disorder: A network-based analysis

Background: Several epidemiological studies and psychological models have suggested that major depressive disorder (MDD) with anhedonia is associated with suicidal ideation (SI). However, little is known about whether the functional network pattern and intrinsic topologically disrupted in patients with anhedonia are related to SI. Methods: The resting-fMRI by applying network-based statistic (NBS) and graph-theory analyses was estimated in 273 patients with MDD (144 high anhedonia [HA], 129 low anhedonia [LA]) and 150 healthy controls. In addition, we quantified the SI scores of each patient. Finally, the mediation analysis assessed whether anhedonia symptoms could mediate the relationship between anhedonia-related network metrics and SI. Result: The NBS analysis demonstrated that individuals with HA have a single abnormally increased functional connectivity component in a frontal-limbic circuit (termed the “anhedonia-related network”, including the frontal cortex, striatum, anterior cingulate cortex and amygdala). The graph-theory analysis demonstrated that the anhedonia-related network showed a significantly disrupted topological organization (lower gamma and lambda), which the small-world property trend randomized. Furthermore, the anhedonia symptoms could mediate the relationship between the anhedonia-related network metrics (the mean functional connectivity values, the area under the curves values of gamma and nodal local efficiency in nucleus accumbens) and SI. Conclusions: We found that disruption of the reward-related network in MDD leads to SI through anhedonia symptoms. These findings show the abnormal topological construction of functional brain network organization in anhedonia, shedding light on the neurological processes underlying SI in MDD patients with anhedonia symptoms

Thermal, mechanical and magnetic properties of functionalized magnetite/vinyl ester nanocomposites

Magnetite (Fe3O4) nanoparticles grafted with thiol groups through silanization of (3-mercaptopropyl) trimethoxy-silane (Fe3O4-SH) were used for preparing vinyl ester resin (VER) nanocomposites with different Fe3O4 nanoparticle loading levels. The calculated thiol group graft percentage of only ∼2.25% did show a significant effect on the physicochemical properties of VER nanosuspensions and nanocomposites. The exothermal curing peak temperature was shifted from 80 °C for pure VER to 75 °C for liquid VER with 10 wt% Fe3O4-SH. The tensile strength (72.6 MPa) of 5 wt% Fe3O4-SH reinforced nanocomposites was increased by 26.3% as compared with that (57.5 MPa) of pure VER composites. However, the tensile strength (62.7 MPa) of 5 wt% Fe3O4 was just increased by 9.0%. The polymer matrix and surface coating were observed to have negligible effects on the magnetic properties of nanoparticles, exhibiting superparamagnetic behaviors

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field