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A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity 期刊论文
NATURE, 2020, 577 (7790) : 416-+
作者:  Morley, Jessica;  Cowls, Josh;  Taddeo, Mariarosaria;  Floridi, Luciano
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

Humoral immune responses to immunization and infection and susceptibilities to antibody-mediated autoimmunity are generally lower in males(1-3). However, the mechanisms underlying such sexual dimorphism are not well understood. Here we show that there are intrinsic differences between the B cells that produce germinal centres in male and female mice. We find that antigen-activated male B cells do not position themselves as efficiently as female B cells in the centre of follicles in secondary lymphoid organs, in which germinal centres normally develop. Moreover, GPR174-an X-chromosome-encoded G-protein-coupled receptor-suppresses the formation of germinal centres in male, but not female, mice. This effect is intrinsic to B cells, and correlates with the GPR174-enhanced positioning of B cells towards the T-cell-B-cell border of follicles, and the distraction of male, but not female, B cells from S1PR2-driven follicle-centre localization. Biochemical fractionation of conditioned media that induce B-cell migration in a GPR174-dependent manner identifies CCL21 as a GPR174 ligand. In response to CCL21, GPR174 triggers a calcium flux and preferentially induces the migration of male B cells  GPR174 also becomes associated with more G alpha i protein in male than in female B cells. Male B cells from orchidectomized mice exhibit impaired GPR174-mediated migration to CCL21, and testosterone treatment rescues this defect. Female B cells from testosterone-treated mice exhibit male-like GPR174-G alpha i association and GPR174-mediated migration. Deleting GPR174 from male B cells causes more efficient positioning towards the follicular centre, the formation of more germinal centres and an increased susceptibility to B-cell-dependent experimental autoimmune encephalomyelitis. By identifying GPR174 as a receptor for CCL21 and demonstrating its sex-dependent control of B-cell positioning and participation in germinal centres, we have revealed a mechanism by which B-cell physiology is fine-tuned to impart sexual dimorphism to humoral immunity.


  
Microbial bile acid metabolites modulate gut ROR gamma(+) regulatory T cell homeostasis 期刊论文
NATURE, 2020, 577 (7790) : 410-+
作者:  Bhargava, Manjul
收藏  |  浏览/下载:18/0  |  提交时间:2020/07/03

The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules(1). Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins(2). Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors(3,4). These receptors have pivotal roles in shaping host innate immune responses(1,5). However, the effect of this host-microorganism biliary network on the adaptive immune system remains poorly characterized. Here we report that both dietary and microbial factors influence the composition of the gut BA pool and modulate an important population of colonic FOXP3(+) regulatory T (T-reg) cells expressing the transcription factor ROR gamma. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this T-reg cell population. Restoration of the intestinal BA pool increases colonic ROR gamma(+) T-reg cell counts and ameliorates host susceptibility to inflammatory colitis via BA nuclear receptors. Thus, a pan-genomic biliary network interaction between hosts and their bacterial symbionts can control host immunological homeostasis via the resulting metabolites.


  
Non-volatile electric control of spin-charge conversion in a SrTiO3 Rashba system 期刊论文
NATURE, 2020, 580 (7804) : 483-+
作者:  Collombet, Samuel;  Ranisavljevic, Noemie;  Nagano, Takashi;  Varnai, Csilla;  Shisode, Tarak;  Leung, Wing;  Piolot, Tristan;  Galupa, Rafael;  Borensztein, Maud;  Servant, Nicolas;  Fraser, Peter;  Ancelin, Katia;  Heard, Edith
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

The polarization direction of a ferroelectric-like state can be used to control the conversion of spin currents into charge currents at the surface of strontium titanate, a non-magnetic oxide.


After 50 years of development, the technology of today'  s electronics is approaching its physical limits, with feature sizes smaller than 10 nanometres. It is also becoming clear that the ever-increasing power consumption of information and communication systems(1) needs to be contained. These two factors require the introduction of non-traditional materials and state variables. As recently highlighted(2), the remanence associated with collective switching in ferroic systems is an appealing way to reduce power consumption. A promising approach is spintronics, which relies on ferromagnets to provide non-volatility and to generate and detect spin currents(3). However, magnetization reversal by spin transfer torques(4) is a power-consuming process. This is driving research on multiferroics to achieve low-power electric-field control of magnetization(5), but practical materials are scarce and magnetoelectric switching remains difficult to control. Here we demonstrate an alternative strategy to achieve low-power spin detection, in a non-magnetic system. We harness the electric-field-induced ferroelectric-like state of strontium titanate (SrTiO3)(6-9) to manipulate the spin-orbit properties(10) of a two-dimensional electron gas(11), and efficiently convert spin currents into positive or negative charge currents, depending on the polarization direction. This non-volatile effect opens the way to the electric-field control of spin currents and to ultralow-power spintronics, in which non-volatility would be provided by ferroelectricity rather than by ferromagnetism.


  
Electrical manipulation of a topological antiferromagnetic state 期刊论文
NATURE, 2020, 580 (7805) : 608-+
作者:  Chabon, Jacob J.;  Hamilton, Emily G.;  Kurtz, David M.;  Esfahani, Mohammad S.;  Moding, Everett J.;  Stehr, Henning;  Schroers-Martin, Joseph;  Nabet, Barzin Y.;  Chen, Binbin;  Chaudhuri, Aadel A.;  Liu, Chih Long;  Hui, Angela B.;  Jin, Michael C.;  Azad, Tej D.;  Almanza, Diego;  Jeon, Young-Jun;  Nesselbush, Monica C.;  Keh, Lyron Co Ting;  Bonilla, Rene F.;  Yoo, Christopher H.;  Ko, Ryan B.;  Chen, Emily L.;  Merriott, David J.;  Massion, Pierre P.;  Mansfield, Aaron S.;  Jen, Jin;  Ren, Hong Z.;  Lin, Steven H.;  Costantino, Christina L.;  Burr, Risa;  Tibshirani, Robert;  Gambhir, Sanjiv S.;  Berry, Gerald J.;  Jensen, Kristin C.;  West, Robert B.;  Neal, Joel W.;  Wakelee, Heather A.;  Loo, Billy W., Jr.;  Kunder, Christian A.;  Leung, Ann N.;  Lui, Natalie S.;  Berry, Mark F.;  Shrager, Joseph B.;  Nair, Viswam S.;  Haber, Daniel A.;  Sequist, Lecia V.;  Alizadeh, Ash A.;  Diehn, Maximilian
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

Room-temperature electrical switching of a topological antiferromagnetic state in polycrystalline Mn3Sn thin films is demonstrated using the same protocol as that used for conventional ferromagnetic metals.


Electrical manipulation of phenomena generated by nontrivial band topology is essential for the development of next-generation technology using topological protection. A Weyl semimetal is a three-dimensional gapless system that hosts Weyl fermions as low-energy quasiparticles(1-4). It has various exotic properties, such as a large anomalous Hall effect (AHE) and chiral anomaly, which are robust owing to the topologically protected Weyl nodes(1-16). To manipulate such phenomena, a magnetic version of Weyl semimetals would be useful for controlling the locations of Weyl nodes in the Brillouin zone. Moreover, electrical manipulation of antiferromagnetic Weyl metals would facilitate the use of antiferromagnetic spintronics to realize high-density devices with ultrafast operation(17,18). However, electrical control of a Weyl metal has not yet been reported. Here we demonstrate the electrical switching of a topological antiferromagnetic state and its detection by the AHE at room temperature in a polycrystalline thin film(19) of the antiferromagnetic Weyl metal Mn3Sn9,10,12,20, which exhibits zero-field AHE. Using bilayer devices composed of Mn3Sn and nonmagnetic metals, we find that an electrical current density of about 10(10) to 10(11) amperes per square metre induces magnetic switching in the nonmagnetic metals, with a large change in Hall voltage. In addition, the current polarity along the bias field and the sign of the spin Hall angle of the nonmagnetic metals-positive for Pt (ref. (21)), close to 0 for Cu and negative for W (ref. (22))-determines the sign of the Hall voltage. Notably, the electrical switching in the antiferromagnet is achieved with the same protocol as that used for ferromagnetic metals(23,24). Our results may lead to further scientific and technological advances in topological magnetism and antiferromagnetic spintronics.


  
An intestinal zinc sensor regulates food intake and developmental growth 期刊论文
NATURE, 2020, 580 (7802) : 263-+
作者:  Wu, Thomas D.;  39;Gorman, William E.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Hodor, an intestinal zinc-gated chloride channel, controls systemic growth in Drosophila by promoting food intake and by modulating Tor signalling and lysosomal homeostasis within enterocytes.


In cells, organs and whole organisms, nutrient sensing is key to maintaining homeostasis and adapting to a fluctuating environment(1). In many animals, nutrient sensors are found within the enteroendocrine cells of the digestive system  however, less is known about nutrient sensing in their cellular siblings, the absorptive enterocytes(1). Here we use a genetic screen in Drosophila melanogaster to identify Hodor, an ionotropic receptor in enterocytes that sustains larval development, particularly in nutrient-scarce conditions. Experiments in Xenopus oocytes and flies indicate that Hodor is a pH-sensitive, zinc-gated chloride channel that mediates a previously unrecognized dietary preference for zinc. Hodor controls systemic growth from a subset of enterocytes-interstitial cells-by promoting food intake and insulin/IGF signalling. Although Hodor sustains gut luminal acidity and restrains microbial loads, its effect on systemic growth results from the modulation of Tor signalling and lysosomal homeostasis within interstitial cells. Hodor-like genes are insect-specific, and may represent targets for the control of disease vectors. Indeed, CRISPR-Cas9 genome editing revealed that the single hodor orthologue in Anopheles gambiae is an essential gene. Our findings highlight the need to consider the instructive contributions of metals-and, more generally, micronutrients-to energy homeostasis.


  
Self-coalescing flows in microfluidics for pulse-shaped delivery of reagents 期刊论文
NATURE, 2019, 574 (7777) : 228-+
作者:  Gokce, Onur;  Castonguay, Samuel;  Temiz, Yuksel;  Gervais, Thomas;  Delamarche, Emmanuel
收藏  |  浏览/下载:0/0  |  提交时间:2019/11/27
Targeting the CBM complex causes T-reg cells to prime tumours for immune checkpoint therapy 期刊论文
NATURE, 2019, 570 (7759) : 112-+
作者:  Di Pilato, Mauro;  Kim, Edward Y.;  Cadilha, Bruno L.;  Prussmann, Jasper N.;  Nasrallah, Mazen N.;  Seruggia, Davide;  Usmani, Shariq M.;  Misale, Sandra;  Zappulli, Valentina;  Carrizosa, Esteban;  Mani, Vinidhra;  Ligorio, Matteo;  Warner, Ross D.;  Medoff, Benjamin D.;  Marangoni, Francesco;  Villani, Alexandra-Chloe;  Mempel, Thorsten R.
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27
Catch shares slow the race to fish 期刊论文
NATURE, 2017, 544 (7649) : 223-+
作者:  Birkenbach, Anna M.;  Kaczan, David J.;  Smith, Martin D.
收藏  |  浏览/下载:2/0  |  提交时间:2019/11/27