bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lactobacillus rhamnosus GG improves cognitive impairments in mice with sepsis
Authors: Wang Linxiao , Zhao Rui , Li Xuemei , Shao Pei , Xie Jiangang , Su Xiangni , Xu Sijia , Huang Yang , Hu Shanbo 
Published: May 2024

Background
Survivors of sepsis may encounter cognitive impairment following their recovery from critical condition. At present, there is no standardized treatment for addressing sepsis-associated encephalopathy. Lactobacillus rhamnosus GG (LGG) is a prevalent bacterium found in the gut microbiota and is an active component of probiotic supplements. LGG has demonstrated to be associated with cognitive improvement. This study explored whether LGG administration prior to and following induced sepsis could ameliorate cognitive deficits, and explored potential mechanisms.

Methods
Female C57BL/6 mice were randomly divided into three groups: sham surgery, cecal ligation and puncture (CLP), and CLP+LGG. Cognitive behavior was assessed longitudinally at 7-9d, 14-16d, and 21-23d after surgery using an open field test and novel object recognition test. The impact of LGG treatment on pathological changes, the expression level of brain-derived neurotrophic factor (BDNF), and the phosphorylation level of the TrkB receptor (p-TrkB) in the hippocampus of mice at two weeks post-CLP (16d) were evaluated using histological, immunofluorescence, immunohistochemistry, and western blot analyses.

Results
The CLP surgery induced and sustained cognitive impairment in mice with sepsis for a minimum of three weeks following the surgery. Compared to mice subjected to CLP alone, the administration of LGG improved the survival of mice with sepsis and notably enhanced their cognitive functioning. Moreover, LGG supplementation significantly alleviated the decrease in hippocampal BDNF expression and p-TrkB phosphorylation levels caused by sepsis, preserving neuronal survival and mitigating the pathological changes within the hippocampus of mice with sepsis. LGG supplementation mitigates sepsis-related cognitive impairment in mice and preserves BDNF expression and p-TrkB levels in the hippocampus.
Using linkage information to weight a genome‐wide association of bipolar disorder
Authors: Howrigan D.P. , Laird N.M. , Smoller J.W. , Devlin B. , McQueen M.B. 
Published: April 2011

AbstractIssues of multiple‐testing and statistical significance in genome‐wide association studies (GWAS) have prompted statistical methods utilizing prior data to increase the power of association results. Using prior findings from genome‐wide linkage studies on bipolar disorder (BPD), we employed a weighted false discovery approach (wFDR; [Roeder et al. 2006. Am J Hum Genet 78(2): 243–252]) to previously reported GWAS data drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD). Using this method, association signals are up or down‐weighted given the linkage score in that genomic region. Although no SNPs in our sample reached genome‐wide significance through the wFDR approach, the strongest single SNP result from the original GWAS results (rs4939921 in myosin VB) is strongly up‐weighted as it occurs on a linkage peak of chromosome 18. We also identify regions on chromosome 9, 17, and 18 where modestly associated SNP clusters coincide with strong linkage scores, implicating them as possible candidate regions for further analysis. Moving forward, we believe the application of prior linkage information will be increasingly useful to future GWAS studies that incorporate rarer variants into their analysis. © 2011 Wiley‐Liss, Inc.
Alkyne Insertion into the MP and MH Bonds (M=Pd, Ni, Pt, and Rh): A Theoretical Mechanistic Study of the CP and CH Bond‐Formation Steps
Authors: Ananikov Valentine P. , Beletskaya Irina P. 
Published: April 2011

AbstractIn hydrogen‐metal‐phosphorus (HMP) transition metal complexes (proposed as intermediates of HP bond addition to alkynes in the catalytic hydrophosphorylation, hydrophosphinylation, and hydrophospination reactions), alkyne insertion into the metal‐hydrogen bond was found much more facile compared to alkyne insertion into the metal‐phosphorus bond. The conclusion was verified for different metals (Pd, Ni, Pt, and Rh), ligands, and phosphorus groups at various theory levels (B3LYP, B3PW91, BLYP, MP2, and ONIOM). The relative reactivity of the metal complexes in the reaction with alkynes was estimated and decreased in the order of Ni>Pd>Rh>Pt. A trend in relative reactivity was established for various types of phosphorus groups: PR2>P(O)R2>P(O)(OR)2, which showed a decrease in rate upon increasing the number of the oxygen atoms attached to the phosphorus center.
Geometrical and Electronic Rules in Fullerene‐Based Compounds
Authors: Gan Li‐Hua , An Jie , Pan Fu‐Sheng , Chang Qing , Liu Zuo‐Hua , Tao Chang‐Yuan 
Published: April 2011

AbstractThe discovery of buckminsterfullerene C60 opened up a new scientific area and stimulated the development of nanoscience and nanotechnology directly. Fullerene science has since emerged to include fullerenes, endohedral fullerenes (mainly metallofullerenes), exofullerenes, and carbon nanotubes as well. Herein, we look back at the development of fullerene science from the perspective of epistemology by highlighting the proposed main rules or criteria for understanding and predicting the structures and stability of fullerene‐based compounds. We also point out that a rule or criterion may contribute significantly to the corresponding discipline and suggest that two unsolved issues in fullerene science are the addition patterns of fullerene derivatives and the structures and stability of nonclassical fullerenes.
Facile Fabrication of Anatase TiO2 Microspheres on Solid Substrates and Surface Crystal Facet Transformation from {001} to {101}
Authors: Zhang Haimin , Liu Porun , Li Feng , Liu Hongwei , Wang Yun , Zhang Shanqing , Guo Mingxing , Cheng Huiming , Zhao Huijun 
Published: April 2011

AbstractAnatase TiO2 microspheres with controlled surface morphologies and exposed crystal facets were directly synthesized on metal titanium foil substrates by means of a facile, one‐pot hydrothermal method without use of any templating reagent. The obtained products were characterized using X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray photoelecron spectroscopy (XPS), and the focused ion beam (FIB) technique. The sizes of the resultant microspheres ranged from 1.1 to 2.1 μm. The transformation of anatase TiO2 microspheres with exposed {001} facets surface to nanosheets surface with {101} facets was achieved by simply controlling the hydrothermal reaction time. The anatase TiO2 microspheres with exposed square‐shaped plane {001} facets were obtained by controlling the reaction time at 1 h. The prolonged reaction time transforms the anatase TiO2 microspheres with exposed square‐shaped plane {001} facets to eroded {001} facets then to a nanosheet surface with exposed {101} facets. With hydrothermal synthesis, the surface morphological structure and crystal facets formation are highly dependent on dissolution/deposition processes, which can be strongly influenced by attributes, such as pH of the reaction media, the total concentration of dissolved and suspended titanium species, and the concentration of fluoride in the reaction solution. The changes of these attributes during the hydrothermal process were therefore measured and used to illustrate the morphology and crystal‐facet transformation processes of anatase TiO2 microspheres. The surface morphologies and crystal‐facet transformations during hydrothermal processes were found to be governed by the compositional changes of the reaction media, driven by dynamically shifted dissolution/deposition equilibria. The photocatalytic activities of the photoanodes made of anatase TiO2 microspheres were evaluated. The experimental results demonstrated that the photocatalytic activity of anatase TiO2 microspheres with exposed {001} facets was found to be 1.5 times higher than that of the anatase TiO2 microspheres with exposed {101} facets.
General Copper‐Catalyzed Transformations of Functional Groups from Arylboronic Acids in Water
Authors: Yang Haijun , Li Yong , Jiang Min , Wang Junmei , Fu Hua 
Published: April 2011

AbstractA simple and general copper‐catalyzed method has been developed for transformations of various functional groups (I, N3, SO2R, OH, NH2, and NO2) on aromatic rings from arylboronic acids in water under air. The protocol uses cheap and readily available inorganic salts (KI, NaN3, NaSO2R, NaOH, NaNO2) and aqueous ammonia as the functional‐group sources, simple Cu2O/NH3 as the catalyst system, environmentally friendly water as the solvent, and oxygen in air as the oxidant. Importantly, the copper catalyst system in water was recyclable. This study should provide a useful strategy for interconversions of the functional groups on aromatic rings.
ChemInform Abstract: Ternary Rare‐Earth Bismuthides Ln5SiBi2 and Ln5GeBi2 (Ln: La—Nd, Ge—Er): Stabilization of the β‐Yb5Sb3‐Type Structure Through Tetrel Substitution.
Authors: Barry Stephen D. , Tkachuk Andriy V. , Bie Haiying , Blanchard Peter E. R. , Mar Arthur 
Published: April 2011

AbstractThe title compounds are prepared by arc‐melting stoichiometric mixtures of the elements with a 5—7 wt.% excess of Bi followed by annealing at 800 °C for at least two weeks.
ChemInform Abstract: Crystal‐Chemistry of Mullite‐Type Aluminoborates Al18B4O33 and Al5BO9: A Stoichiometry Puzzle.
Authors: Fisch Martin , Armbruster Thomas , Rentsch Daniel , Libowitzky Eugen , Pettke Thomas 
Published: April 2011

AbstractOrthorhombic Al2O3‐rich aluminoborate samples are synthesized by solid state reactions between α‐Al2O3 and B2O3 or H3BO3 (Pt crucible, 1100—1200 °C).
ChemInform Abstract: K3BiAs6Se12: A Two‐Dimensional Bismuth Selenoarsenate Containing Crown‐Shaped Anions [As3Se6]3‐.
Authors: Wu Yuandong , Bensch Wolfgang 
Published: April 2011

AbstractSingle crystals of K3BiAs6Se12 are prepared from mixtures of K2Se3, Bi, As2Se3, and Se in molar ratios of 1:1:1.5:2 (540 °C, 5 d).
ChemInform Abstract: Na27Ru14O48: A New Mixed‐Valence Sodium Ruthenate with Magnetic Heptameric Plaquettes.
Authors: Allred J. M. , Wang L. M. , Khalifah P. , Cava R. J. 
Published: April 2011

AbstractSingle crystals of the title compound are prepared by reaction of Na2CO3 and RuO2 (alumina crucible, air, 700 °C, 3 d).
ChemInform Abstract: Desymmetrizations of meso‐tert‐Norbornenols by Rhodium(I)‐Catalyzed Enantioselective Retro‐Allylations.
Authors: Waibel Michael , Cramer Nicolai 
Published: April 2011

AbstractSubtle differences of the substrate structure and, more importantly, of the conditions for the title transformation lead to diverging pathways.
ChemInform Abstract: Synthesis of Dienes by Palladium‐Catalyzed Couplings of Tosylhydrazones with Aryl and Alkenyl Halides.
Authors: Barluenga Jose , Tomas‐Gamasa Maria , Aznar Fernando , Valdes Carlos 
Published: April 2011

AbstractTosylhydrazones generated in situ from α,β‐unsaturated ketones and tosylhydrazine give with aryl halides cyclic or acyclic dienes.
ChemInform Abstract: A Recyclable Fluoroalkylated 1,4‐Disubstituted [1,2,3]‐triazole Organocatalyst for Aldol Condensation of Aldehydes and Ketones.
Authors: Zhu Yi‐Wei , Yi Wen‐Bin , Cai Chun 
Published: April 2011

AbstractFluoroalkylated 1,4‐disubstituted [1,2,3]‐triazoles are shown to be good catalysts for the aldol condensation of aldehydes and ketones.
ChemInform Abstract: The Use of Bromotrichloromethane in Chlorination Reactions.
Authors: Newman Stephen G. , Bryan Christopher S. , Perez Didier , Lautens Mark 
Published: April 2011

AbstractThe combination of (II) and PPh3 is used as efficient system to convert aldehydes and ketones into geminal dichloroalkenes and benzyl alcohols into benzyl chlorides.
ChemInform Abstract: Facile Synthesis of (E)‐Alkenyl Aldehydes from Allyl Arenes or Alkenes via Pd(II)‐Catalyzed Direct Oxygenation of Allylic C—H Bond.
Authors: Chen Huoji , Jiang Huanfeng , Cai Congbi , Dong Jia , Fu Wei 
Published: April 2011

AbstractThe reaction is applied to a variety of allyl arenes.
ChemInform Abstract: Indium‐Mediated Microwave‐Assisted One‐Pot Synthesis of α,β‐Unsaturated Amides.
Authors: Feng Sunlin , Jiang Shilei , Zhang Zhiying , Yu Xiaochun 
Published: April 2011

AbstractAn economic, simple, efficient, and stereoselective method for the title synthesis is developed.
ChemInform Abstract: Ionic Liquid Supported Organotin Reagents: Green Tools for Stille Cross‐Coupling Reactions with Brominated Substrates.
Authors: Louaisil Nicolas , Pham Phuoc Dien , Boeda Fabien , Faye Djibril , Castanet Anne‐Sophie , Legoupy Stephanie 
Published: April 2011

AbstractSubstituted organotin reagents supported on ionic liquid are used for Stille cross‐coupling reactions.
ChemInform Abstract: Robust Hole Transport in a Thienothiophene Derivative Toward Low‐Cost Electronics.
Authors: Oku Shinya , Takamiya Kazuhiro , Adachi Daisuke , Ishikawa Shuhei , Nagamatsu Shuichi , Takashima Wataru , Hayase Shuzi , Kaneto Keiichi 
Published: April 2011

AbstractSynthesis and electron transport characteristics of p‐type organic semiconductor (III) are reported.
ChemInform Abstract: Efficient Preparation of Polyfunctional Indoles via a Zinc Organometallic Variation of the Fischer Indole Synthesis.
Authors: Zhang Zhi‐Guang , Haag Benjamin A. , Li Jin‐Shan , Knochel Paul 
Published: April 2011

AbstractFunctionalized organozinc substrates are prepared following different metalation strategies and subjected to the reaction with various aryldiazonium salts.
ChemInform Abstract: Diarylprolinol Silyl Ether Catalyzed Asymmetric Friedel—Crafts Alkylation of Indoles with α,β‐Unsaturated Aldehydes: Enhanced Enantioselectivity and Mechanistic Investigations.
Authors: Shi Zi‐Hui , Sheng Hao , Yang Ke‐Fang , Jiang Jian‐Xiong , Lai Guo‐Qiao , Lu Yixin , Xu Li‐Wen 
Published: April 2011

AbstractThis improved method offers substantial advantages over traditional approaches such as avoiding the use of acids or bases and the high level of stereoselectivity.
ChemInform Abstract: Conventional as well as Microwave‐Assisted Synthesis and Antimicrobial Screening of 4‐Aryl‐3‐chloro‐1‐[(5‐nitroindazol‐1‐yl)acetamido]‐2‐oxo‐azetidines.
Authors: Upadhyay Apoorva , Srivastava S. K. , Sricastava S. D. , Yadav R. 
Published: April 2011

AbstractSome of the new 2‐oxoazetidines (VIII) (12 examples) exhibit significant antibacterial and antifungal activity.
ChemInform Abstract: Preparation of Quaternary Ammonium Salts with a Perhydroimidazo[1,5‐c]oxazolium Molecular Skeleton.
Authors: Korepin A. G. , Galkin P. V. , Glushakova N. M. , Malygina V. S. , Perepelkina E. K. , Lagodzinskaya G. V. , Eremenko L. T. 
Published: April 2011

AbstractMannich reaction of bis(nitroxymethyl)oxazolidine (I) is found to furnish quaternary ammonium salt (IV) with unique structure instead of the expected Mannich bases.
ChemInform Abstract: Synthesis of Azide‐Alkyne Fragments for “Click” Chemical Applications. Formation of Chiral 1,4‐Disubstituted‐(β‐alkyl)‐γ‐1,2,3‐triazole Scaffolds from Orthogonally Protected Chiral β‐Alkyl‐trialkylsilyl‐γ‐pentynyl Azides and Chiral β‐Alkyl‐γ‐pentynyl‐alcohols.
Authors: Montagnat Oliver D. , Lessene Guillaume , Hughes Andrew B. 
Published: April 2011

AbstractThe new azides (IX) and alcohols such as (X) are coupled by Huisgen 1,3‐dipolar cycloaddition to give chiral 1,4‐disubstituted triazole derivatives.
ChemInform Abstract: Reaction of Guanidine with peri‐Substituted (R‐Ethynyl)‐9,10‐anthraquinones Bearing Electron‐Donating Substituents.
Authors: Baranov D. S. , Vasilevsky S. F. 
Published: April 2011

AbstractThe title reactions results in the predominant or exclusive formation of 2‐amino‐3‐aroyldibenzoquinolinones.
ChemInform Abstract: Synthesis of 4‐(3H)‐Quinazolinones by Microwave Assisted Tandem Reaction and Evaluation of Their Antibacterial and Antifungal Activities.
Authors: Priya M. Gnana Ruba , Zulykama Y. , Girija K. , Murugesh S. , Perumal P. T. 
Published: April 2011

AbstractA one‐pot synthesis of quinazolinone derivatives (IV) (10 examples) from anthranilic acid, primary aromatic amines and Vilsmeier reagent is developed.
ChemInform Abstract: Rhodium(I)‐Catalyzed 1,4‐Silicon Shift of Unactivated Silanes from Aryl to Alkyl: Enantioselective Synthesis of Indanol Derivatives.
Authors: Seiser Tobias , Cramer Nicolai 
Published: April 2011

AbstractA Caryl—Si bond activation and 1,4‐Si shift of unactivated tetraorganylsilanes is readily achieved in the presence of chiral Rh—difluorphos complex to give silylmethylindanols, e.g. (II), in good stereoselectivities (up to 99% e.e.
ChemInform Abstract: Triterpene Glycosides and Glucosyl Esters, and a Triterpene from the Leaves of Schefflera actinophylla.
Authors: Wanas Amira Samir , Matsunami Katsuyoshi , Otsuka Hideaki , Desoukey Samar Yahie , Fouad Mostafa Ahmed , Kamel Mohamed Salah 
Published: April 2011

Abstract3 New ursane‐type triterpene glycosides (I), 2 new lupane‐type triterpene glucosides (II) and (IIIa), one new lupane‐type triterpene (IIIb), and one new lupane‐type triterpene glucosyl ester (IIIc) are isolated from the EtOAc and BuOH fractions of the leaves of the title evergreen tree.
ChemInform Abstract: Antibacterial Sphingolipid and Steroids from the Black Coral Antipathes dichotoma.
Authors: Al‐Lihaibi Sultan Samran , Ayyad Seif‐Eldin Nasr , Shaher Fekry , Alarif Walied Mohamed 
Published: April 2011

AbstractThe 2 new compounds (I) and (II) are isolated from the black coral Antipathes dichotoma together with 3 known compounds.
ChemInform Abstract: Nortriterpenoids and Lignans from the Fruit of Schisandra chinensis.
Authors: Xue Yong‐Bo , Zhang Yan‐Long , Yang Jian‐Hong , Du Xue , Pu Jian‐Xin , Zhao Wei , Li Xiao‐Nian , Xiao Wei‐Lie , Sun Han‐Dong 
Published: April 2011

AbstractPhytochemical investigation of the fruit of Schisandra chinensis led to the isolation of 7 new compounds together with 16 known compounds.
ChemInform Abstract: The Natural Product Hybrid (I) of Syringolin A and Glidobactin A Synergizes Proteasome Inhibition Potency with Subsite Selectivity.
Authors: Clerc Jerome , Li Nan , Krahn Daniel , Groll Michael , Bachmann Andre S. , Florea Bogdan I. , Overkleeft Herman S. , Kaiser Markus 
Published: April 2011

Abstractsynthesis and bioactivity of title compound (I)
ChemInform Abstract: Synthesis and Structure—Active Relationship of 1‐Aryl‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline Anticonvulsants.
Authors: Gitto Rosaria , De Luca Laura , Ferro Stefania , Agnello Stefano , Russo Emilio , De Sarro Giovanbattista , Chimirri Alba 
Published: April 2011

AbstractA series of 6 title compounds of type (I) are prepared.
Endothelium‐coated tumor clusters are associated with poor prognosis and micrometastasis of hepatocellular carcinoma after resection
Authors: Ding Tong , Xu Jing , Zhang Ying , Guo Rong‐Ping , Wu Wen‐Chao , Zhang Shao‐Dan , Qian Chao‐Nan , Zheng Limin 
Published: April 2011

AbstractBACKGROUND:Distinct morphologic features of microvascular endothelium exist in tumor tissues. The objective of this study was to investigate the prognostic value of endothelium‐coated tumor clusters (ECTCs) in hepatocellular carcinoma (HCC).METHODS:ECTCs were evaluated by immunohistochemical staining for cluster of differentiation 34 (CD34) (a cell surface glycoprotein which is expressed specifically on tumor microvascular endothelium in HCC) in 239 specimens from patients with primary HCC. Overall survival (OS) and time to recurrence (TTR) were determined using Kaplan‐Meier analysis and a Cox proportional hazards regression model. Levels of terminal deoxynucleotide transferase‐mediated deoxyuridine triphosphate nick‐end labeling (TUNEL) staining, and Ki‐67 expression, and E‐cadherin expression were assessed to determine tumor apoptosis, proliferation, and invasiveness, respectively.RESULTS:The presence of ECTCs was associated with a poor prognosis in all patients and in patient subgroups stratified by tumor size, TNM classification, and Barcelona Clinic Liver Cancer stage and tumor invasiveness. In a multivariate Cox proportional hazards analysis, the presence of ECTCs emerged as an independent prognostic indicator of both poor OS (P = .001; hazard ratio, 1.949) and shorter TTR (P < .001; hazard ratio, 2.085). Furthermore, the presence of ECTCs was associated with micrometastatic endothelium‐coated emboli (P < .001; chi‐square test) and early relapse after resection (P < .001; chi‐square test). In addition, patients who had endothelium‐coated emboli, in which tumor cells displayed high proliferation and low apoptosis, had poor OS and shorter TTR.CONCLUSIONS:The current results suggested that the presence of ECTCs was an efficient, simple, and convenient predictor of a poor prognosis in patients with HCC that potentially may serve as a novel target for the prevention and treatment of HCC metastasis. Cancer 2011;. © 2011 American Cancer Society.
Rapamycin‐sensitive signals control TCR/CD28‐driven Ifng, Il4 and Foxp3 transcription and promoter region methylation
Authors: Tomasoni Romana , Basso Veronica , Pilipow Karolina , Sitia Giovanni , Saccani Simona , Agresti Alessandra , Mietton Flore , Natoli Gioacchino , Colombetti Sara , Mondino Anna 
Published: April 2011

AbstractThe mammalian target of rapamycin (mTOR) controls T‐cell differentiation in response to polarizing cytokines. We previously found that mTOR blockade by rapamycin (RAPA) delays the G1‐S cell cycle transition and lymphocyte proliferation. Here, we report that both mTOR complex 1 and mTOR complex 2 are readily activated following TCR/CD28 engagement and are critical for early expression of Ifng, Il4 and Foxp3, and for effector T cell differentiation in the absence of polarizing cytokines. While inhibition of mTOR complex 1 and cell division were evident at low doses of RAPA, inhibition of mTOR complex 2, Ifng, Il4 and Foxp3 expression, and T‐cell polarization required higher doses and more prolonged treatments. We found that while T‐bet and GATA3 were readily induced following TCR/CD28 engagement, administration of RAPA delayed their expression, and interfered with the loss of DNA methylation within Ifng and Il4 promoter regions. In contrast, RAPA prevented activation‐dependent DNA methylation of the Foxp3 promoter favoring Foxp3 expression. As a result, RAPA‐cultured cells lacked immediate effector functions and instead were enriched for IL‐2+ cells. We propose that mTOR‐signaling, by timing the expression of critical transcription factors and DNA methylation of proximal promoter regions, regulates transcriptional competence at immunologically relevant sites and hence lymphocyte differentiation.
Setting the threshold for extra‐thymic differentiation of Foxp3+ Tregs: TGF‐β‐dependent and T‐cell autonomous
Authors: Godkin Andrew , Gallimore Awen 
Published: April 2011

AbstractThere is a lack of clarity regarding the conditions supporting de novo induction of Tregs. While there is widespread agreement in the literature over the need for optimal stimulation conditions and exogenous TGF‐β in vitro, a number of studies indicate that sub‐immunogenic conditions induce Tregs in vivo. These seemingly disparate findings have hindered the ability to pin down the conditions promoting Treg induction, including the role of co‐stimulation and even the necessity for TGF‐β. Two studies in this issue of the European Journal of Immunology re‐examine these previous findings in detail and shed some light on the controversy. These studies demonstrate that Treg induction depends on reaching a certain threshold of signal strength: the requirement for co‐stimulation is therefore not absolute but dictated by the strength of other signals received by the T cell. Furthermore, these studies demonstrate that the only source of TGF‐β required for the induction of Tregs under sub‐optimal condition is the T cells themselves. Overall, the picture that emerges is one where sub‐immunogenicity, rather than a requirement for exogenous TGF‐β, defines the conditions that support TGF‐β‐dependent Foxp3 induction in a T‐cell autonomous fashion. The next challenge lies in utilizing this knowledge for the purpose of inducing Tregs for therapeutic gain.