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1.
Cell ; 166(3): 567-581, 2016 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-27374329

RESUMEN

Insulin signaling regulates many facets of animal physiology. Its dysregulation causes diabetes and other metabolic disorders. The spindle checkpoint proteins MAD2 and BUBR1 prevent precocious chromosome segregation and suppress aneuploidy. The MAD2 inhibitory protein p31(comet) promotes checkpoint inactivation and timely chromosome segregation. Here, we show that whole-body p31(comet) knockout mice die soon after birth and have reduced hepatic glycogen. Liver-specific ablation of p31(comet) causes insulin resistance, hyperinsulinemia, glucose intolerance, and hyperglycemia and diminishes the plasma membrane localization of the insulin receptor (IR) in hepatocytes. MAD2 directly binds to IR and facilitates BUBR1-dependent recruitment of the clathrin adaptor AP2 to IR. p31(comet) blocks the MAD2-BUBR1 interaction and prevents spontaneous clathrin-mediated IR endocytosis. BUBR1 deficiency enhances insulin sensitivity in mice. BUBR1 depletion in hepatocytes or the expression of MAD2-binding-deficient IR suppresses the metabolic phenotypes of p31(comet) ablation. Our findings establish a major IR regulatory mechanism and link guardians of chromosome stability to nutrient metabolism.


Asunto(s)
Puntos de Control del Ciclo Celular , Insulina/metabolismo , Mitosis , Transducción de Señal , Complejo 2 de Proteína Adaptadora/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Aneuploidia , Animales , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Segregación Cromosómica , Clatrina/metabolismo , Endocitosis , Células Hep G2 , Homeostasis , Humanos , Resistencia a la Insulina , Hígado/metabolismo , Proteínas Mad2/metabolismo , Ratones , Ratones Noqueados , Proteínas Nucleares , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor de Insulina/metabolismo
2.
Cell ; 164(1-2): 69-80, 2016 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-26724866

RESUMEN

Long noncoding RNAs (lncRNAs) have emerged as regulators of diverse biological processes. Here, we describe the initial functional analysis of a poorly characterized human lncRNA (LINC00657) that is induced after DNA damage, which we termed "noncoding RNA activated by DNA damage", or NORAD. NORAD is highly conserved and abundant, with expression levels of approximately 500-1,000 copies per cell. Remarkably, inactivation of NORAD triggers dramatic aneuploidy in previously karyotypically stable cell lines. NORAD maintains genomic stability by sequestering PUMILIO proteins, which repress the stability and translation of mRNAs to which they bind. In the absence of NORAD, PUMILIO proteins drive chromosomal instability by hyperactively repressing mitotic, DNA repair, and DNA replication factors. These findings introduce a mechanism that regulates the activity of a deeply conserved and highly dosage-sensitive family of RNA binding proteins and reveal unanticipated roles for a lncRNA and PUMILIO proteins in the maintenance of genomic stability.


Asunto(s)
Inestabilidad Genómica , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/metabolismo , Animales , Secuencia de Bases , Inestabilidad Cromosómica , Células HCT116 , Humanos , Ratones , Ploidias , ARN Largo no Codificante/química , ARN Largo no Codificante/genética
3.
Mol Cell ; 83(16): 2856-2871.e8, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37536339

RESUMEN

Cohesin and CCCTC-binding factor (CTCF) are key regulatory proteins of three-dimensional (3D) genome organization. Cohesin extrudes DNA loops that are anchored by CTCF in a polar orientation. Here, we present direct evidence that CTCF binding polarity controls cohesin-mediated DNA looping. Using single-molecule imaging, we demonstrate that a critical N-terminal motif of CTCF blocks cohesin translocation and DNA looping. The cryo-EM structure of the cohesin-CTCF complex reveals that this CTCF motif ahead of zinc fingers can only reach its binding site on the STAG1 cohesin subunit when the N terminus of CTCF faces cohesin. Remarkably, a C-terminally oriented CTCF accelerates DNA compaction by cohesin. DNA-bound Cas9 and Cas12a ribonucleoproteins are also polar cohesin barriers, indicating that stalling may be intrinsic to cohesin itself. Finally, we show that RNA-DNA hybrids (R-loops) block cohesin-mediated DNA compaction in vitro and are enriched with cohesin subunits in vivo, likely forming TAD boundaries.


Asunto(s)
Cromatina , Estructuras R-Loop , Factor de Unión a CCCTC/genética , Factor de Unión a CCCTC/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , ADN/genética , ADN/metabolismo , Cohesinas
5.
Nature ; 584(7820): 304-309, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32581365

RESUMEN

The human GABAB receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction1. A unique GPCR that is known to require heterodimerization for function2-6, the GABAB receptor has two subunits, GABAB1 and GABAB2, that are structurally homologous but perform distinct and complementary functions. GABAB1 recognizes orthosteric ligands7,8, while GABAB2 couples with G proteins9-14. Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail15. Although the VFT heterodimer structure has been resolved16, the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABAB receptor, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique 'intersubunit latch' within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.


Asunto(s)
Microscopía por Crioelectrón , Receptores de GABA-B/química , Receptores de GABA-B/ultraestructura , Calcio/metabolismo , Etanolaminas/química , Etanolaminas/metabolismo , Humanos , Ligandos , Modelos Moleculares , Fosforilcolina/química , Fosforilcolina/metabolismo , Dominios Proteicos , Multimerización de Proteína , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Receptores de GABA-B/metabolismo , Relación Estructura-Actividad
6.
Mol Cell ; 70(3): 395-407.e4, 2018 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-29727616

RESUMEN

Telomeres and telomere-binding proteins form complex secondary nucleoprotein structures that are critical for genome integrity but can present serious challenges during telomere DNA replication. It remains unclear how telomere replication stress is resolved during S phase. Here, we show that the BUB3-BUB1 complex, a component in spindle assembly checkpoint, binds to telomeres during S phase and promotes telomere DNA replication. Loss of the BUB3-BUB1 complex results in telomere replication defects, including fragile and shortened telomeres. We also demonstrate that the telomere-binding ability of BUB3 and kinase activity of BUB1 are indispensable to BUB3-BUB1 function at telomeres. TRF2 targets BUB1-BUB3 to telomeres, and BUB1 can directly phosphorylate TRF1 and promote TRF1 recruitment of BLM helicase to overcome replication stress. Our findings have uncovered previously unknown roles for the BUB3-BUB1 complex in S phase and shed light on how proteins from diverse pathways function coordinately to ensure proper telomere replication and maintenance.


Asunto(s)
Proteínas de Ciclo Celular/genética , Replicación del ADN/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas Serina-Treonina Quinasas/genética , Telómero/genética , Línea Celular , Línea Celular Tumoral , ADN Helicasas/genética , Células HEK293 , Células HeLa , Humanos , Puntos de Control de la Fase M del Ciclo Celular/genética , Fase S/genética , Huso Acromático/genética , Proteínas de Unión a Telómeros/genética
7.
Mol Cell ; 70(6): 1134-1148.e7, 2018 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-29932904

RESUMEN

Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin's ATPase activity and loading. Moreover, Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin's initial association with loading sites. Lastly, Scc2 mutations that permit loading in the absence of Scc4 increase Scc2's association with chromosomal cohesin and reduce that of Pds5. We suggest that cohesin switches between two states: one with Pds5 bound that is unable to hydrolyze ATP efficiently but is capable of release from chromosomes and another in which Scc2 replaces Pds5 and stimulates ATP hydrolysis necessary for loading and translocation from loading sites.


Asunto(s)
Adenosina Trifosfatasas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Adenosina Trifosfatasas/genética , Proteínas de Ciclo Celular/genética , Cromátides/genética , Cromátides/metabolismo , Proteínas Cromosómicas no Histona/genética , Segregación Cromosómica , ADN de Hongos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Cohesinas
8.
Proc Natl Acad Sci U S A ; 120(19): e2219098120, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37126725

RESUMEN

Graphene oxide (GO) membranes with nanoconfined interlayer channels theoretically enable anomalous nanofluid transport for ultrahigh filtration performance. However, it is still a significant challenge for current GO laminar membranes to achieve ultrafast water permeation and high ion rejection simultaneously, because of the contradictory effect that exists between the water-membrane hydrogen-bond interaction and the ion-membrane electrostatic interaction. Here, we report a vertically aligned reduced GO (VARGO) membrane and propose an electropolarization strategy for regulating the interfacial hydrogen-bond and electrostatic interactions to concurrently enhance water permeation and ion rejection. The membrane with an electro-assistance of 2.5 V exhibited an ultrahigh water permeance of 684.9 L m-2 h-1 bar-1, which is 1-2 orders of magnitude higher than those of reported GO-based laminar membranes. Meanwhile, the rejection rate of the membrane for NaCl was as high as 88.7%, outperforming most reported graphene-based membranes (typically 10 to 50%). Molecular dynamics simulations and density-function theory calculations revealed that the electropolarized VARGO nanochannels induced the well-ordered arrangement of nanoconfined water molecules, increasing the water transport efficiency, and thereby resulting in improved water permeation. Moreover, the electropolarization effect enhanced the surface electron density of the VARGO nanochannels and reinforced the interfacial attractive interactions between the cations in water and the oxygen groups and π-electrons on the VARGO surface, strengthening the ion-partitioning and Donnan effect for the electrostatic exclusion of ions. This finding offers an electroregulation strategy for membranes to achieve both high water permeability and high ion rejection performance.

9.
Mol Cell Proteomics ; 22(4): 100524, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36870568

RESUMEN

The heterogeneity of idiopathic pulmonary fibrosis (IPF) limits its diagnosis and treatment. The association between the pathophysiological features and the serum protein signatures of IPF currently remains unclear. The present study analyzed the specific proteins and patterns associated with the clinical parameters of IPF based on a serum proteomic dataset by data-independent acquisition using MS. Differentiated proteins in sera distinguished patients with IPF into three subgroups in signal pathways and overall survival. Aging-associated signatures by weighted gene correlation network analysis coincidently provided clear and direct evidence that aging is a critical risk factor for IPF rather than a single biomarker. Expression of LDHA and CCT6A, which was associated with glucose metabolic reprogramming, was correlated with high serum lactic acid content in patients with IPF. Cross-model analysis and machine learning showed that a combinatorial biomarker accurately distinguished patients with IPF from healthy individuals with an area under the curve of 0.848 (95% CI = 0.684-0.941) and validated from another cohort and ELISA assay. This serum proteomic profile provides rigorous evidence that enables an understanding of the heterogeneity of IPF and protein alterations that could help in its diagnosis and treatment decisions.


Asunto(s)
Fibrosis Pulmonar Idiopática , Proteómica , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Proteínas Sanguíneas , Biomarcadores , Chaperonina con TCP-1
10.
Nano Lett ; 24(9): 2876-2884, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38385324

RESUMEN

Upconversion (UC)/downconversion (DC)-luminescent lanthanide-doped nanocrystals (LDNCs) with near-infrared (NIR, 650-1700 nm) excitation have been gaining increasing popularity in bioimaging. However, conventional NIR-excited LDNCs cannot be degraded and eliminated eventually in vivo owing to intrinsic "rigid" lattices, thus constraining clinical applications. A biodegradability-tunable heterogeneous core-shell-shell luminescent LDNC of Na3HfF7:Yb,Er@Na3ZrF7:Yb,Er@CaF2:Yb,Zr (abbreviated as HZC) was developed and modified with oxidized sodium alginate (OSA) for multimode bioimaging. The dynamic "soft" lattice-Na3Hf(Zr)F7 host and the varying Zr4+ doping content in the outmoster CaF2 shell endowed HZC with tunable degradability. Through elaborated core-shell-shell coating, Yb3+/Er3+-coupled UC red and green and DC second near-infrared (NIR-II) emissions were, respectively, enhanced by 31.23-, 150.60-, and 19.42-fold when compared with core nanocrystals. HZC generated computed tomography (CT) imaging contrast effects, thus enabling NIR-II/CT/UC trimodal imaging. OSA modification not only ensured the exemplary biocompatibility of HZC but also enabled tumor-specific diagnosis. The findings would benefit the clinical imaging translation of LDNCs.


Asunto(s)
Elementos de la Serie de los Lantanoides , Nanopartículas , Hafnio , Circonio , Nanopartículas/química , Tomografía Computarizada por Rayos X
11.
J Biol Chem ; 299(11): 105296, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37774974

RESUMEN

3D chromatin organization plays a critical role in regulating gene expression, DNA replication, recombination, and repair. While initially discovered for its role in sister chromatid cohesion, emerging evidence suggests that the cohesin complex (SMC1, SMC3, RAD21, and SA1/SA2), facilitated by NIPBL, mediates topologically associating domains and chromatin loops through DNA loop extrusion. However, information on how conformational changes of cohesin-NIPBL drive its loading onto DNA, initiation, and growth of DNA loops is still lacking. In this study, high-speed atomic force microscopy imaging reveals that cohesin-NIPBL captures DNA through arm extension, assisted by feet (shorter protrusions), and followed by transfer of DNA to its lower compartment (SMC heads, RAD21, SA1, and NIPBL). While binding at the lower compartment, arm extension leads to the capture of a second DNA segment and the initiation of a DNA loop that is independent of ATP hydrolysis. The feet are likely contributed by the C-terminal domains of SA1 and NIPBL and can transiently bind to DNA to facilitate the loading of the cohesin complex onto DNA. Furthermore, high-speed atomic force microscopy imaging reveals distinct forward and reverse DNA loop extrusion steps by cohesin-NIPBL. These results advance our understanding of cohesin by establishing direct experimental evidence for a multistep DNA-binding mechanism mediated by dynamic protein conformational changes.


Asunto(s)
Proteínas de Ciclo Celular , Proteínas Cromosómicas no Histona , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , ADN/química , Cromatina , Cohesinas
12.
Plant Biotechnol J ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037027

RESUMEN

As an essential macronutrient, phosphorus (P) is often a limiting nutrient because of its low availability and mobility in soils. Drought is a major environmental stress that reduces crop yield. How plants balance and combine P-starvation responses (PSRs) and drought resistance is unclear. In this study, we identified the transcription factor ZmPHR1 as a major regulator of PSRs that modulates phosphate (Pi) signaling and homeostasis. We found that maize zmphr1 mutants had reduced P concentration and were sensitive to Pi starvation, whereas ZmPHR1-OE lines displayed elevated Pi concentration and yields. In addition, 57% of PSR genes and nearly 70% of ZmPHR1-regulated PSR genes in leaves were transcriptionally responsive to drought. Under moderate and early drought conditions, the Pi concentration of maize decreased, and PSR genes were up-regulated before drought-responsive genes. The ZmPHR1-OE lines exhibited drought-resistant phenotypes and reduced stomatal apertures, whereas the opposite was true of the zmphr1 mutants. ZmPT7-OE lines and zmspx3 mutants, which had elevated Pi concentration, also exhibited drought resistance, but zmpt7 mutants were sensitive to drought. Our results suggest that ZmPHR1 plays a central role in integrating Pi and drought signals and that Pi homeostasis improves the ability of maize to combat drought.

13.
PLoS Comput Biol ; 19(11): e1011598, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37956217

RESUMEN

In contrast to heart failure (HF) with reduced ejection fraction (HFrEF), effective interventions for HF with preserved ejection fraction (HFpEF) have proven elusive, in part because it is a heterogeneous syndrome with incompletely understood pathophysiology. This study utilized mathematical modeling to evaluate mechanisms distinguishing HFpEF and HFrEF. HF was defined as a state of chronically elevated left ventricle end diastolic pressure (LVEDP > 20mmHg). First, using a previously developed cardiorenal model, sensitivities of LVEDP to potential contributing mechanisms of HFpEF, including increased myocardial, arterial, or venous stiffness, slowed ventricular relaxation, reduced LV contractility, hypertension, or reduced venous capacitance, were evaluated. Elevated LV stiffness was identified as the most sensitive factor. Large LV stiffness increases alone, or milder increases combined with either decreased LV contractility, increased arterial stiffness, or hypertension, could increase LVEDP into the HF range without reducing EF. We then evaluated effects of these mechanisms on mechanical signals of cardiac outward remodeling, and tested the ability to maintain stable EF (as opposed to progressive EF decline) under two remodeling assumptions: LV passive stress-driven vs. strain-driven remodeling. While elevated LV stiffness increased LVEDP and LV wall stress, it mitigated wall strain rise for a given LVEDP. This suggests that if LV strain drives outward remodeling, a stiffer myocardium will experience less strain and less outward dilatation when additional factors such as impaired contractility, hypertension, or arterial stiffening exacerbate LVEDP, allowing EF to remain normal even at high filling pressures. Thus, HFpEF heterogeneity may result from a range of different pathologic mechanisms occurring in an already stiffened myocardium. Together, these simulations further support LV stiffening as a critical mechanism contributing to elevated cardiac filling pressures; support LV passive strain as the outward dilatation signal; offer an explanation for HFpEF heterogeneity; and provide a mechanistic explanation distinguishing between HFpEF and HFrEF.


Asunto(s)
Insuficiencia Cardíaca , Hipertensión , Humanos , Volumen Sistólico/fisiología , Corazón , Miocardio/patología , Hipertensión/complicaciones
14.
Environ Sci Technol ; 58(31): 14034-14041, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39048519

RESUMEN

For electrochemical application in seawater or brine, continuous scaling on cathodes will form insulation layers, making it nearly impossible to run an electrochemical reaction continuously. Herein, we report our discovery that a cathode consisting of conical nanobundle arrays with hydrophobic surfaces exhibits a unique scaling-free function. The hydrophobic surfaces will be covered with microbubbles created by electrolytic water splitting, which limits scale crystals from standing only on nanotips of conical nanobundles, and the bursting of large bubbles formed by the accumulation of microbubbles will cause a violent disturbance, removing scale crystals automatically from nanotips. Benefiting from the scaling-free properties of the cathode, high-purity nano-CaCO3 (98.9%) and nano-Mg(OH)2 (99.5%) were extracted from seawater. This novel scaling-free cathode is expected to eliminate the inherent limitations of electrochemical technology and open up a new route to seawater mining.


Asunto(s)
Carbonato de Calcio , Electrodos , Agua de Mar , Agua de Mar/química , Carbonato de Calcio/química , Hidróxido de Magnesio/química , Técnicas Electroquímicas
15.
Mol Cell ; 61(4): 489-491, 2016 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-26895420

RESUMEN

Recent studies, including two in this issue of Molecular Cell (Elbatsh et al., 2016; Beckouët et al., 2016), cast light on how cohesin regulators harness the energy of ATP hydrolysis to open the cohesin ring and enable dynamic, regulated entrapment of chromosomes.

16.
Mol Cell ; 62(2): 248-259, 2016 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-26971492

RESUMEN

The ring-shaped cohesin complex regulates transcription, DNA repair, and chromosome segregation by dynamically entrapping chromosomes to promote chromosome compaction and sister-chromatid cohesion. The cohesin ring needs to open and close to allow its loading to and release from chromosomes. Cohesin dynamics are controlled by the releasing factors Pds5 and Wapl and the cohesin stabilizer Sororin. Here, we report the crystal structure of human Pds5B bound to a conserved peptide motif found in both Wapl and Sororin. Our structure establishes the basis for how Wapl and Sororin antagonistically influence cohesin dynamics. The structure further reveals that Pds5 can bind inositol hexakisphosphate (IP6). The IP6-binding segment of Pds5B is shaped like the jaw of a plier lever and inhibits the binding of Scc1 to Smc3. We propose that Pds5 stabilizes a transient, open state of cohesin to promote its release from chromosomes.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Cromosomas Humanos/metabolismo , Proteínas de Unión al ADN/metabolismo , Ácido Fítico/metabolismo , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Sitios de Unión , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular/química , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Proteínas Cromosómicas no Histona/química , Cromosomas Humanos/química , Cromosomas Humanos/genética , Secuencia Conservada , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Células HeLa , Humanos , Cinética , Modelos Moleculares , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Proteínas Proto-Oncogénicas/metabolismo , Interferencia de ARN , Relación Estructura-Actividad , Factores de Transcripción/química , Factores de Transcripción/genética , Transfección , Cohesinas
17.
Int J Mol Sci ; 25(14)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39063080

RESUMEN

Exhaustive exercise is known to induce muscle damage characterized by inflammation and oxidative stress. Although "regular" and "weekend warrior" exercise regimens have been shown to confer comparable health benefits in human studies, such as reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality, their differential impacts on muscle damage post-exhaustive exercise remain unclear. This study aimed to compare the effects of long-term, moderate-intensity (LTMI) and short-term, high-intensity (STHI) training modalities, matched for total exercise volume, on gut microbiota, short-chain fatty acids (SCFAs), and exhaustive exercise-induced muscle damage in mice, as well as to evaluate the correlation between these factors. LTMI is considered a regular exercise regimen, while STHI shares some similarities with the "weekend warrior" pattern, such as promoting exercise intensity and condensing training sessions into a short period. Our findings indicate that LTMI training significantly enhanced the abundance of SCFA-producing bacteria, including Akkermansia, Prevotellaceae_NK3B31_group, Odoribacter, Alistipes, and Lactobacillus, thereby increasing SCFA levels and attenuating muscle damage following exhaustive swimming. In contrast, STHI training increased the abundance of opportunistic pathogens such as Staphylococcus and Bilophila, without altering SCFA levels, and was associated with exacerbated muscle damage. Moreover, we observed a significant negative correlation between the abundance of SCFA-producing bacteria and SCFA levels with the expression of inflammatory cytokines in the muscle of mice post-exhaustive exercise. Conversely, the abundance of Staphylococcus and Bilophila showed a notable positive correlation with these cytokines. Additionally, the effects of LTMI and STHI on exhaustive exercise-induced muscle damage were transmissible to untrained mice via fecal microbiota transplantation, suggesting that gut microbiota changes induced by these training modalities may contribute to their contrasting impacts on muscle damage. These results underscore the significance of selecting an appropriate training modality prior to engaging in exhaustive exercise, with implications for athletic training and injury prevention.


Asunto(s)
Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Músculo Esquelético , Condicionamiento Físico Animal , Animales , Ratones , Músculo Esquelético/metabolismo , Ácidos Grasos Volátiles/metabolismo , Masculino , Estrés Oxidativo , Ratones Endogámicos C57BL , Natación
18.
Angew Chem Int Ed Engl ; 63(30): e202406452, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38735843

RESUMEN

Acidic H2O2 synthesis through electrocatalytic 2e- oxygen reduction presents a sustainable alternative to the energy-intensive anthraquinone oxidation technology. Nevertheless, acidic H2O2 electrosynthesis suffers from low H2O2 Faradaic efficiencies primarily due to the competing reactions of 4e- oxygen reduction to H2O and hydrogen evolution in environments with high H+ concentrations. Here, we demonstrate the significant effect of alkali metal cations, acting as competing ions with H+, in promoting acidic H2O2 electrosynthesis at industrial-level currents, resulting in an effective current densities of 50-421 mA cm-2 with 84-100 % Faradaic efficiency and a production rate of 856-7842 µmol cm-2 h-1 that far exceeds the performance observed in pure acidic electrolytes or low-current electrolysis. Finite-element simulations indicate that high interfacial pH near the electrode surface formed at high currents is crucial for activating the promotional effect of K+. In situ attenuated total reflection Fourier transform infrared spectroscopy and ab initio molecular dynamics simulations reveal the central role of alkali metal cations in stabilizing the key *OOH intermediate to suppress 4e- oxygen reduction through interacting with coordinated H2O.

19.
Yeast ; 40(11): 540-549, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37818980

RESUMEN

Five yeast strains isolated from tree bark and rotten wood collected in central and southwestern China, together with four Brazilian strains (three from soil and rotting wood collected in an Amazonian rainforest biome and one from Bromeliad collected in Alagoas state) and one Costa Rican strain isolated from a flower beetle, represent a new species closely related with Yueomyces sinensis in Saccharomycetaceae, as revealed by the 26S ribosomal RNA gene D1/D2 domain and the internal transcribed spacer region sequence analysis. The name Yueomyces silvicola sp. nov. is proposed for this new species with the holotype China General Microbiological Culture Collection Center 2.6469 (= Japan Collection of Microorganisms 34885). The new species exhibits a whole-genome average nucleotide identity value of 77.8% with Y. sinensis. The two Yueomyces species shared unique physiological characteristics of being unable to utilize ammonium and the majority of the amino acids, including glutamate and glutamine, as sole nitrogen sources. Among the 20 amino acids tested, only leucine and tyrosine can be utilized by the Yueomyces species. Genome sequence comparison showed that GAT1, which encodes a GATA family protein participating in transcriptional activation of nitrogen-catabolic genes in Saccharomyces cerevisiae, is absent in the Yueomyces species. However, the failure of the Yueomyces species to utilize ammonium, glutamate, and glutamine, which are generally preferred nitrogen sources for microorganisms, implies that more complicated alterations in the central nitrogen metabolism pathway might occur in the genus Yueomyces.


Asunto(s)
Compuestos de Amonio , Saccharomycetales , Saccharomyces cerevisiae/genética , Glutamina/genética , Ácido Glutámico/genética , Filogenia , ADN Espaciador Ribosómico/genética , Análisis de Secuencia de ADN , Saccharomycetales/genética , Aminoácidos/genética , ADN de Hongos/genética
20.
Environ Sci Technol ; 57(1): 615-625, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36525305

RESUMEN

Graphene is promising in the construction of next-generation nanofiltration membranes for wastewater treatment and water purification. However, the application of graphene-based membranes has still been prohibited by their deficiencies in permeability and ion rejection. Herein, regulating the 2D channel and enhancing the charge density are co-adopted for simultaneous enhancement of the water flux and salt rejection of reduced graphene oxide (rGO) membranes through the intercalation of molybdenum sulfide (MoS2) nanosheets and external electrical assistance. The fabricated rGO/MoS2 membranes possess expanded nanochannels with less friction and a higher water molecule transport velocity gradient (from 8.57 to 14.07 s-1) than those of rGO membranes. Consequently, their water permeance increases from 0.92 to 34.9 L m-2 h-1 bar-1. Meanwhile, benefiting from the high capacitance and negative potential of -1.1 V versus the saturated calomel electrode given to the membranes, their rejection rates toward NaCl reach 87.2% and those toward Na2SO4 reach 93.7%. The Donnan steric pore model analysis indicates that the capacitively and electrically increased surface charge density make great contributions to the higher ion rejection rate. This work gives new insights into membrane design for high water flux and salt rejection efficiency.


Asunto(s)
Grafito , Molibdeno , Agua
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