GJ (gap junction) channels mediate direct intercellular communication and play an important role in many physiological processes. Six connexins oligomerize to form a hemichannel and two hemichannels ...dock together end-to-end to form a GJ channel. Connexin extracellular domains (E1 and E2) have been shown to be important for the docking, but the molecular mechanisms behind the docking and formation of GJ channels are not clear. Recent developments in atomic GJ structure and functional studies on a series of connexin mutants revealed that E1 and E2 are likely to play different roles in the docking. Non-covalent interactions at the docking interface, including hydrogen bonds, are predicted to form between interdocked extracellular domains. Protein sequence alignment analysis on the docking compatible/incompatible connexins indicate that the E1 domain is important for the formation of the GJ channel and the E2 domain is important in the docking compatibility in heterotypic channels. Interestingly, the hydrogen-bond forming or equivalent residues in both E1 and E2 domains are mutational hot spots for connexin-linked human diseases. Understanding the molecular mechanisms of GJ docking can assist us to develop novel strategies in rescuing the disease-linked connexin mutants.
Excessive exposure to manganese in the environment or workplace is strongly linked to neurodegeneration and cognitive impairment, but the precise pathogenic mechanism and preventive measures are ...still not fully understood. The study aimed to investigate manganese -induced oxidative damage in the nervous system from an epigenetic perspective, focusing on the H3K36ac-dependent antioxidant pathway. Additionally, it sought to examine the potential of curcumin in preventing manganese-induced oxidative damage. Histopathology and transmission electron microscopy revealed that apoptosis and necrosis of neurons and mitochondrial ultrastructure damage were observed in the striatum of manganese-exposed rats. manganese suppressed the expression of mitochondrial antioxidant genes, leading to oxidative damage in the rats' striatum and SH-SY5Y cells. With higher doses of manganese, levels of histone acetyltransferase lysine acetyltransferase 2 A (KAT2A) expression and H3K36ac level decreased. ChIP-qPCR confirmed that H3K36ac enrichment in the promoter regions of antioxidant genes SOD2, PRDX3, and TXN2 was reduced in SH-SY5Y cells after manganese exposure, leading to decreased expression of these genes. Overexpression of KAT2A confirms that it attenuates manganese-induced mitochondrial oxidative damage by regulating H3K36ac levels, which in turn controls the expression of antioxidant genes SOD2, PRDX3, and TXN2 in the manganese-exposed cell model. Furthermore, curcumin might control H3K36ac levels by influencing KAT2A expression, boosting antioxidant genes expression, and reducing manganese-induced mitochondrial oxidative damage. In conclusion, the regulation of mitochondrial oxidative stress by histone acetylation may be an important mechanism of manganese-induced neurotoxicity. This regulation could be achieved by reducing the level of H3K36ac near the promoter region of mitochondrial-associated antioxidant genes via KAT2A. Curcumin mitigates manganese-induced oxidative damage in mitochondria and plays a crucial protective role in manganese-induced oxidative injury in the nervous system.
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•Manganese causes mitochondrial oxidative damage in rat striatum and SH-SY5Y cells.•KAT2A inhibits the levels of mitochondrial antioxidant genes by reducing H3K36ac level.•Curcumin attenuates mitochondrial oxidative damage by raising H3K36ac level via KAT2A.
Global Monsoon Dynamics and Climate Change Zhisheng, An; Guoxiong, Wu; Jianping, Li ...
Annual review of earth and planetary sciences,
01/2015, Letnik:
43, Številka:
1
Journal Article
Recenzirano
This article provides a comprehensive review of the global monsoon that encompasses findings from studies of both modern monsoons and paleomonsoons. We introduce a definition for the global monsoon ...that incorporates its three-dimensional distribution and ultimate causes, emphasizing the direct drive of seasonal pressure system changes on monsoon circulation and depicting the intensity in terms of both circulation and precipitation. We explore the global monsoon climate changes across a wide range of timescales from tectonic to intraseasonal. Common features of the global monsoon are global homogeneity, regional diversity, seasonality, quasi-periodicity, irregularity, instability, and asynchroneity. We emphasize the importance of solar insolation, Earth orbital parameters, underlying surface properties, and land-air-sea interactions for global monsoon dynamics. We discuss the primary driving force of monsoon variability on each timescale and the relationships among dynamics on multiple timescales. Natural processes and anthropogenic impacts are of great significance to the understanding of future global monsoon behavior.
•Full-band phonon Monte Carlo simulation is conducted to study thermal spreading resistance in GaN HEMTs.•Different simulation approaches for simulation phonon transport in GaN HEMTs are thoroughly ...compared.•Incorporating first-principle-calculated phonon properties in device thermal simulations is essential.
Accurate thermal simulation is essential for the near-junction thermal management and electro-thermal co-design of GaN HEMTs. While various methods have been employed to simulate phonon thermal transport in GaN, a comprehensive evaluation of their performance and reliability has yet to be conducted. In this work, first-principle-based steady-state full-band phonon tracing Monte Carlo (MC) simulations are conducted to study the thermal spreading resistance in GaN HEMTs. The results of full-band MC serve as a standard against which the applicability, accuracy, and computational efficiency of three widely-used approaches to simulate the near-junction phonon transport in GaN are thoroughly examined. The simulation techniques compared in this study include MC simulations with empirical isotropic phonon dispersion (isotropic MC), MC simulations with gray-medium approximation (gray MC), and finite-element methods (FEM) with effective thermal conductivities (FEM with keff). It is found that isotropic MC largely overestimates the thermal resistance due to the empirical model’s overestimation of phonon mean free path (MFP) distributions. By selecting an appropriate average MFP, gray MC can approximate the full-band results well, but due to its inability to reflect the contributions of different phonon modes, discrepancies are inevitable for some geometric parameters. For FEM-based analysis, although the diffusive nature of Fourier’s law precludes the reproduction of channel temperature distributions, the influence of phonon ballistic effects on the junction temperature can be accurately reflected in the well-chosen effective thermal conductivities. The comparison highlights the importance of directly incorporating first-principles-calculated phonon properties into device thermal simulations, and the paper can provide a clearer understanding of near-junction thermal transport in GaN and can be useful for thermal simulations of GaN-based devices.
Abstract
To investigate the effect of ellagic acid (EA) treatment on immune function in burned rats. First, 30 Sprague-Dawley rats were established as a deep second-degree burn model. They were ...randomly divided into three groups: Model group, EA 50 mg/kg, and EA 100 mg/kg group. The wound area of rats at 0–7 days was measured and the wound healing rate was calculated. The levels of inflammatory factors tumor necrosis factor-α (TNF-α), interferon γ (IFN-γ), interleukin (IL)-1β, IL-6, IL-10, and immunoglobulins IgA, IgG, and IgM in rat serum were evaluated by ELISA. Flow cytometry was used to detect the CD4 +/CD8 + T cell ratio, levels of Foxp3 + Treg cells, and CD4 + CD25 + regulatory T cells (Treg) cells levels in the peripheral blood of rats. On the fourth to seventh day of the burn, EA treatment could significantly promote the decrease of the wound area and the increase of the wound healing rate in burned rats. Further examination revealed that the levels of inflammatory factors in serum were remarkedly decreased and immunoglobulins levels were increased in the EA group, compared with the Model group. Meanwhile, the levels of CD4 + CD25 + Treg cells and Foxp3+ Treg cells were significantly decreased, whereas the CD4+/CD8 + T cell ratio was observably increased in a concentration-dependent manner. Altogether, EA effectively promotes the wound healing of burned rats by regulating the levels of inflammatory factors, immunoglobulin, and T cells in burned rats, and improves the symptoms of burn immunosuppression.
The expansion of inland Asia deserts has considerably influenced the environmental, social and economic activities in Asia. Aridification of inland Asia, especially timing of the initiation of Asian ...desertification, is a contentious topic in paleoclimatology. Late Cenozoic eolian loess-red clay sequences on the Chinese Loess Plateau, which possess abundant paleoclimatic and paleo-environmental information, can be regarded as an indicator of inland Asia desertification. Here we present a detailed magnetostratigraphic investigation of a new red clay sequence about 654 m in Zhuanglang located at the western Chinese Loess Plateau. Sedimentological, geochemical, mineralogical, and quartz morphological lines of evidence show that the red clay is of eolian origin. Magnetostratigraphic correlations indicate that this core sequence spans from 25.6 to 4.8 Ma, and typical eolian red clay appears as early as 25 Ma. This extends the lower limit of the red clay on the Chinese Loess Plateau from the previously thought early Miocene back into the late Oligocene. This new red clay record further implies that the inland Asia desertification was initiated at least by the late Oligocene. This sequence provides a unique high-resolution geological record for understanding the inland Asia desertification process since the late Oligocene.
Schistosomiasis, also called bilharziasis, is a neglected tropical disease induced by schistosomes that infects hundreds of millions of people worldwide. In the life cycle of schistosomiasis, eggs ...are regarded as the main pathogenic factor, causing granuloma formation in the tissues and organs of hosts, which can cause severe gastrointestinal and liver granulomatous immune responses and irreversible fibrosis. Increasing evidence suggests that the gut microbiome influences the progression of schistosomiasis and plays a central role in liver disease via the gut-liver axis. When used as pharmaceutical supplements or adjunctive therapy, probiotics have shown promising results in preventing, mitigating, and even treating schistosomiasis. This review elucidates the potential mechanisms of this three-way parasite-host-microbiome interaction by summarizing schistosome-mediated intestinal flora disorders, local immune changes, and host metabolic changes, and elaborates the important role of the gut microbiome in liver disease after schistosome infection through the gut-liver axis. Understanding the mechanisms behind this interaction may aid in the discovery of probiotics as novel therapeutic targets and sustainable control strategies for schistosomiasis.
Environmental conditions in one of Earth's most densely populated regions, East Asia, are dominated by the monsoon. While Quaternary monsoon variability is reasonably well understood, pre-Quaternary ...monsoon variability and dynamics remain enigmatic. In particular, little is known about potential relationships between northern hemispheric monsoon response and major Cenozoic changes in Antarctic ice cover. Here we document long-term East Asian summer monsoon (EASM) intensification through the Late Miocene–Pliocene (∼8.2 to 2.6 Ma), and attribute this to progressive Antarctic glaciation. Our new high-resolution magnetic records of long-term EASM intensification come from the Late Miocene–Pliocene Red Clay sequence on the Chinese Loess Plateau; we identify underlying mechanisms using a numerical climate-model simulation of EASM response to an idealized stepwise increase in Antarctic ice volume. We infer that progressive Antarctic glaciation caused intensification of the cross-equatorial pressure gradient between an atmospheric high-pressure cell over Australia and a low-pressure cell over mid-latitude East Asia, as well as intensification of the cross-equatorial sea-surface temperature (SST) gradient. These combined atmospheric and oceanic adjustments led to EASM intensification. Our findings offer a new and more global perspective on the controls behind long-term Asian monsoon evolution.
•Improved magnetochronology for the Shilou Red Clay on the Chinese Loess Plateau.•New magnetic records of the Late Miocene–Pliocene East Asian Summer monsoon.•East Asian Summer monsoon intensity increases progressively from ∼8 to 2.6 Ma.•Asian monsoon intensification is attributed to increased Antarctic glaciation.
The global climate cyclicity transferred from an Early Pleistocene mode dominated by the obliquity periodicity to a new Middle Pleistocene state dominated by the eccentricity periodicity in the ...absence of any significant changes in orbital forcing, known as the Early–Middle Pleistocene transition (EMPT), is an unresolved issue of Milankovitch orbital theory. Here we contribute new insights into the orbital characteristic and dynamics of the Asian summer monsoon precipitation changes across the EMPT. Spectral analyses of precipitation over the past 1.6 Myr reconstructed from a new loess magnetic susceptibility (χ) stack suggest that the EMPT of the summer monsoon precipitation characterized by a shift from obliquity to eccentricity rhythm occurred over a ~640 kyr long-term period from ~1.24 to 0.6 Ma rather than quasi-instantaneously on a much shorter duration. The eccentricity cyclicity initiated as early as 1.24 Ma, subsequently intensified and became the dominated pacing from 1.1 Ma, while obliquity weakened at ~1.1 Ma and significantly weakened at ~0.7 Ma. These EMPT characteristics of the summer monsoon precipitation reflect complex impacts from global climate systems and regional climate changes in the Northern and Southern Hemispheres, and in both low- and high-latitude regions.
•Pleistocene summer monsoon precipitation reconstruction on the Loess Plateau•Asian summer monsoon shifted gradually from obliquity to eccentricity rhythm.•The dynamics of the Early–Middle Pleistocene transition of Asian summer monsoon
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