Conclusion: Our findings indicate that smooth muscle cells display an altered transcriptome at atherosclerosis-prone locations before actual lesion development. Copyright (C) 2010 S. Karger AG, Basel”
“The present study investigated the contribution of episodic memory processes mediated by the medial temporal lobes to solving open-ended problems: problems for which standard solutions or set procedures for arriving at solutions AZD1080 nmr do not exist. Patients with unilateral temporal lobe epilepsy and excisions (TLE), older adults and control participants were asked to describe detailed solutions to various open-ended, social scenarios. TLE patients and older adults, both having deficits in episodic memory, provided fewer steps relevant

to the given solution than their comparison group. Segmenting the descriptions into details using the methods of the Autobiographical Interview, we also found that patients with TLE and older adults provided fewer internal (episodic) details but a similar number of external (semantic) details compared to their control group. These findings are the first to demonstrate that processes underlying episodic memory, in particular those enabling the retrieval of experiential detail and episodic simulation may contribute to open-ended problem solving. Given that we examined groups with medial temporal lobe lesions and known episodic memory dysfunction, these

results further suggest that the negative consequences of episodic memory loss Ro-3306 manufacturer resulting Selleck Bleomycin from damage to or deterioration of the medial temporal lobes extend beyond that of memory to include other domains, such as problem solving. (C) 2011 Elsevier Ltd. All rights reserved.”
“Background: Extracellular matrix deposition is the main factor inducing stenotic lesions in arterial grafts. Lysyl oxidases (LOX) play a key role in stabilizing collagen and elastin. Objective: To examine the repair response to arterial allografts in terms of LOX expression and collagen/elastin deposition using LOX inhibitors. Methods: Lewis/Fisher-344 rats were used as donors/recipients.

Donor segments were grafted to the right iliac artery of recipients and retrieved 14/30 (short-term) or 90/180 days (long-term) after surgery. One group of animals was injected with a potent irreversible LOX inhibitor daily for 30 days. Results: Intimal hyperplasia increased in thickness until 90/180 days postsurgery. Elastin showed great expression in the neointima at 14/30 days and in the media at 90/180 days. LOX/LOXL1 were similarly expressed in the arterial wall during the first month. In the long term, their overexpression was confined to neointimal layers. At 14 days, collagen types I/III were identified in the grafts. The neointima acquired collagen I over time. In the group of animal treated with the LOX inhibitor, intimal hyperplasia was significantly inhibited. Conclusion: LOX were overexpressed in late stages of intimal hyperplasia in the allografts.

The transfection of miRNA mimics into cultured VSMCs reduced the protein levels of each potential target. Conversely, miRNA inhibitors reduced phosphate and calcium-induced VSMC calcification. Furthermore, these inhibitors decreased the intracellular Ca2+ concentration in cultured VSMCs after treatment

with phosphate and calcium. Our results suggest that increased expression of miR-135a(star), miR-762, miR-714, and miR-712(star) in VSMCs may be involved in VSMC calcification by disrupting Ca2+ efflux proteins. Laboratory Investigation (2012) 92, 1250-1259; doi:10.1038/labinvest.2012.85; Talazoparib clinical trial published online 11 June 2012″
“The serotonin 1(B/D) (5-HT1(B/D)) receptor has shown potential as a target for decreasing aggression. The 5-HT1(B/D) agonist zolmitriptan’s ability to reduce aggressive behavior in humans and its interaction with the well-known aggression-enhancing drug alcohol were examined.

Our objective was to investigate zolmitriptan’s potential to modify human aggression in a laboratory paradigm across a range of

alcohol doses. Alcohol has been consistently associated with aggression and violence, thus we hoped to expand current understanding of alcohol’s role in aggressive behavior via manipulation of the serotonin (5-HT) system.

Eleven social drinkers, seven male, were recruited to Z-IETD-FMK chemical structure participate in a research study lasting 3-4 weeks. Aggression was measured using the point-subtraction aggression paradigm (PSAP), a laboratory model widely used in human aggression studies. Subjects were administered 5-mg zolmitriptan and placebo capsules along with alcohol doses of 0.0, 0.4 and 0.8 g/kg in a within-subject, counterbalanced dosing design. Data were analyzed as the ratio of aggressive/monetary-earning responses, to account for possible changes in overall motor function due to alcohol.

There was a significant alcohol by

zolmitriptan interaction on the aggressive/monetary response ratio. Specifically, compared to placebo, zolmitriptan decreased the aggressive/monetary PRN1371 cell line ratio at the 0.4- and 0.8-g/kg alcohol doses.

A 5-mg dose of zolmitriptan effectively reduced alcohol-related aggression in an acute dosing protocol, demonstrating an interaction of 5-HT and alcohol in human aggressive behavior.”
“Angeli’s salt (Na2N2O3) decomposes into nitroxyl (HNO) and nitrite (NO2-), compounds of physiological and therapeutic interest for their impact on biological signaling both through nitric oxide and nitric oxide independent pathways. Both nitrite and HNO oxidize oxygenated hemoglobin to methemoglobin. Earlier work has shown that HNO catalyzes the reduction of nitrite by deoxygenated hemoglobin. In this work, we have shown that HNO accelerates the oxidation of oxygenated hemoglobin by NO2-.

(C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Chaperonins assist in the folding of nascent and misfolded proteins, though the mechanism of folding within the lumen of the chaperonin remains poorly understood. The archeal chaperonin from Methanococcus marapaludis, Mm-Cpn, shares the eightfold double barrel structure with other group

II chaperonins, including the eukaryotic TRiC/CCT, required for actin and tubulin folding. However, Mm-Cpn is composed of a single species subunit, similar to group I chaperonin GroEL, rather than the eight subunit species needed for TRiC/CCT. Features of the beta-sheet fold have been BTSA1 concentration identified as sites of recognition by group II chaperonins. The crystallins, the major components of the vertebrate eye lens, are

beta-sheet proteins with two homologous Greek key domains. During refolding in vitro a partially folded intermediate is populated, and partitions between productive folding and off-pathway aggregation. We report here that in the presence of physiological concentrations of ATP, Mm-Cpn suppressed the aggregation of H gamma D-Crys by binding the partially folded intermediate. The complex was sufficiently stable to permit recovery by size exclusion chromatography. In the Tariquidar chemical structure presence of ATP, Mm-Cpn promoted the refolding of the H gamma D-Crys intermediates to the native state. The ability of Mm-Cpn to bind and refold a human beta-sheet protein suggests that Mm-Cpn may be useful as a simplified model for the substrate recognition mechanism of TRiC/CCT.”
“Entry of reovirus virions has been well studied in several tissue culture systems. After attachment to junctional adhesion molecule A (JAM-A), virions SN-38 in vitro undergo clathrin-mediated endocytosis followed by proteolytic disassembly of the capsid and penetration to the cytoplasm. However, during in vivo infection of the intestinal tract, and likely in the tumor microenvironment, capsid proteolysis (uncoating) is initiated extracellularly. We used

multiple approaches to determine if uncoated reovirus particles, called intermediate subviral particles (ISVPs), enter cells by directly penetrating the limiting membrane or if they take advantage of endocytic pathways to establish productive infection. We found that entry and infection by reovirus ISVPs was inhibited by dynasore, an inhibitor of dynamin-dependent endocytosis, as well as by genistein and dominant-negative caveolin-1, which block caveolar endocytosis. Inhibition of caveolar endocytosis also reduced infection by reovirus virions. Extraction of membrane cholesterol with methyl-beta-cyclodextrin inhibited infection by virions but had no effect when infection was initiated with ISVPs. We found this pathway to be independent of both clathrin and caveolin.

7 +/- 4.6 x 10(6)/ml and 16.8 +/- 4.4 x 10(6)/ml (p = 0.005), sperm motility was 35.8% +/- 2.7% and 25.4% +/- 2.1% (p = 0.008), and sperm strict morphology was 17.6% +/- 4.4% and 14.8% +/- 4.1% (p = 0.01) of normal sperm, respectively. During the treatment period serum follicle-stimulating hormone levels decreased significantly (p = 0.02) and serum inhibin B concentrations increased significantly (p = 0.01). During the off-drug period semen parameters gradually returned to baseline values but the differences were still significant for sperm density

(p = 0.03) and sperm motility (p = 0.03). The correlation coefficients analysis revealed a positive association between the duration of treatment with ubiquinol and sperm density (r = 0.74, p = 0.017), sperm motility (r = 0.66, p = 0.024) and sperm morphology (r = 0.57, p = 0.027).

Conclusions: Ubiquinol was significantly effective selleck compound in men with unexplained oligoasthenoteratozoospermia for improving sperm density, sperm motility and sperm morphology.”
“In the spinal cord serotonin (5-HT) systems modulate the spinal network via BX-795 datasheet various 5-HT receptors. Serotonin 2A receptor and serotonin 2C receptor

(5-HT2A and 2C receptors) are likely the most important 5-HT receptors for enhancing the motoneuron excitability by facilitating the persistent inward current (PIC), and thus play an important role for the pathogenesis of spasticity after spinal cord injury. In conjunction with our 5-HT2A receptor study, using a same sacral spinal transection rat model we have in this study examined 5-HT2C receptor immunoreactivity (5-HT2CR-IR) changes at seven different time intervals after

spinal injury. We found that 5-HT2CR-IR was widely distributed in different regions of the spinal gray matter and was predominantly located in the neuronal somata and their dendrites although it seemed also present in axonal fibers https://www.selleck.cn/products/ganetespib-sta-9090.html in the superficial dorsal horn. 5-HT2CR-IR in different regions of the spinal gray matter was seen to be increased at 14 days after transection (with an average similar to 1.3-fold higher than in sham-operated group) but did not reach a significant level until at 21 days (similar to 1.4-fold). The increase sustained thereafter and a plateau level was reached at 45 days (similar to 1.7-fold higher), a value similar as that at 60 days. When 5-HT2CR-IR analysis was confined to the ventral horn motoneuron somata (including a proportion of proximal dendrites) a significant increase was not detected until 45 days post-operation. 5-HT2CR upregulation in the spinal gray matter is confirmed with Western blot in the rats 60 days post-operation. The time course of 5-HT2CR upregulation in the spinal gray matter and motoneurons was positively correlated with the development of tail spasticity (clinical scores).

Amphetamine treatment may be harmful in stroke recovery by making the brain more vulnerable to ischaemia. These data also suggest that amphetamine abusers might be more susceptible to cerebral ischaemia. (c) 2013 Elsevier CHIR-99021 concentration Inc. All rights reserved.”
“Transmembrane domains (TMD) connect the inner with the outer world of a living cell Single TMD containing (bitopic) receptors are of particular interest because their oligomerization seems to be a common activation mechanism in cell signaling We analyzed the composition of TMDs in bitopic proteins within the proteomes of 12 model organisms The average number of strongly polar and charged

residues decreases during evolution while the occurrence of a dimerization motif GxxxG remains unchanged This may reflect the avoidance of unspecific binding

within a growing receptor interaction network In addition we propose a new experimental approach for studying helix helix interactions in giant plasma membrane vesicles using scanning PD0332991 fluorescence cross correlation spectroscopy Measuring eGFP/mRFP tagged versions of cytokine receptors confirms the homotypic interactions of the erythropoietin receptor in contrast to the Interleukin 4 receptor chains As a proof of principle by swapping the TMDs the interaction potential of erythropoietin receptor was partially transferred to Interleukin-4 receptor a and vice versa Non interacting receptors can therefore serve as host molecules for TMDs whose oligomerization capability must be assessed Computational analysis of the free energy gain resulting from TMD dimer formation strongly corroborates the experimental findings potentially allowing in silico pre screening of interacting pairs”
“Hypersensitivity

to asparaginase is Epacadostat cell line common, but the differential diagnosis can be challenging and the diagnostic utility of antibody tests is unclear. We studied allergic reactions and serum antibodies to E. coli asparaginase (Elspar) in 410 children treated on St. Jude Total XV protocol for acute lymphoblastic leukemia. Of 169 patients (41.2%) with clinical allergy, 147 (87.0%) were positive for anti-Elspar antibody. Of 241 patients without allergy, 89 (36.9%) had detectable antibody. Allergies (P = 0.0002) and antibodies (P = 6.6 x 10(-6)) were higher among patients treated on the low-risk arm than among those treated on the standard/high-risk arm. Among those positive for antibody, the antibody titers were higher in those who developed allergy than in those who did not (P<1 x 10(-15)). Antibody measures at week 7 of continuation therapy had a sensitivity of 87-88% and a specificity of 68-69% for predicting or confirming clinical reactions. The level of antibodies was inversely associated with serum asparaginase activity (P = 7.0 x 10(-6)). High antibody levels were associated with a lower risk of osteonecrosis (odds ratio = 0.83; 95% confidence interval, 0.78-0.89; P = 0.007).

Recanalization of internal carotid artery (ICA) dissection by stent-assisted thrombolysis has been recently proposed. We report two cases of acute symptomatic ICA dissection with tandem occlusion successfully treated with emergent endovascular stent-assisted thrombolysis using new self-expandable intracranial stents.

A 37-year-old woman and a 59-year-old man were admitted in our hospital

after acute severe symptoms of right-hemispheric selleck chemical stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 15 and 18, respectively. In both cases, magnetic resonance angiography showed tandem occlusion and angiography confirmed tandem occlusion with ICA dissection. An extensive mismatch region was diagnosed by Perfusion-diffusion MRI of the brain within 3 h after symptoms onset. Treatment was initiated 4 h after symptom onset by implantation

of self-expandable intracranial stents into the dissected ICA and administration of intra-arterial recombinant tissue plasminogen activator.

Recanalization of the ICA and middle cerebral artery (MCA) was accomplished within 6 h after symptoms onset. In both cases, no periprocedural complication was observed and follow-up CT scan showed only a mild brain infarct in the MCA territory. After, respectively, 12 and 10 months follow-up, patients had a favorable outcome with NIHSS 0 and mRS a parts per thousand currency sign1.

Endovascular stent-assisted thrombolysis Apoptosis inhibitor appears to be a promising treatment in tandem occlusion due to ICA dissection. Our work underline the potential use LCL161 chemical structure of self-expandable intracranial stents in symptomatic acute ICA dissection.”
“Objectives: Ground-glass opacities are typically difficult to inspect and to palpate during video-assisted

thoracic surgery. We therefore examined whether ultrasonographic assessments could localize ground-glass opacities and help to achieve adequate resection margins.

Methods: An intraoperative ultrasonographic procedure was prospectively performed on 44 patients harboring ground-glass opacities of less than 20 mm in diameter to localize these lesions and to achieve adequate margins. We also examined whether there were any complications resulting from the intraoperative ultrasonogram, such as lung injury, heart injury, or arrhythmia. We excluded patients with both asthma and chronic obstructive pulmonary disease from this study inasmuch as the intraoperative ultrasonographic procedure is more difficult to interpret when residual air is present in the lung.

Results: A total of 53 ground-glass opacities were successfully identified by intraoperative ultrasonography without any complications. Of the 20 mixed ground-glass opacities that we examined, 15 were found on palpation. However, only 4 (12.1%) of the 33 pure ground-glass opacities could be palpated. In all instances in which complete collapse of the lung was achieved (30/53 of these cases), high-quality echo images were obtained.

(C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Objective: Acute tubular necrosis (ATN) secondary to induced warm ischemia (WI) results in inflammatory and delayed fibrotic processes and remains a common clinical problem with serious consequences. Because OSI-027 tumor necrosis factor-a (TNF-alpha) is a prominent proinflammatory factor implicated in the pathophysiology of acute renal ischemia reperfusion injury (IRI), we hypothesized

that FR167653 (FR), a potent inhibitor of TNF-alpha and interleukin-1 beta production, may reduce IRI.

Methods. IRI was induced in male pigs by bilateral clamping of the renal pedicle for 90 minutes (WI90), or unilateral renal clamping (90 minutes) after contralateral nephrectomy (1/2N x 90), or unilateral renal clamping without contralateral nephrectomy (WIuni90). FR was administered intravenously 60 minutes before WI (1 mg/kg/h), during WI, and continuously

for 3 hours (1 mg/kg/h) during reperfusion in treated groups (FRW190, FR1/2N x 90, or FRWIuni90). Blood and urine samples were collected between Verubecestat mouseMK-8931 chemical structure day 1 and 3 months after reperfusion for assessment of renal function. Kidneys were excised and renal tissues were collected at 3 months for morphologic and inflammation evaluation and protein analysis. Experimental groups were compared with sham operated (control) and heminephrectomized (Unif) groups without renal ischemia.

Results. Three WI90 animals (43%)

and five 1/2N x 90 (70%) were euthanized and necropsied at day 7 because of no urine production or poor conditions. Mortality was significantly improved after FR treatment. Survival was 100% in the control, Unif, WIuni90, and FR groups. In Unif groups, PR significantly RO4929097 in vivo reduced renal failure and bilateral renal ischemia (P < .05). At 3 months, proteinuria was significantly reduced in FR-treated groups (P < .01). Inflammatory cells count was also dramatically diminished in FR-treated pigs (P < .01 for CD3-positive cells). The second aspect of transient ischemia is the fibrotic process determined at 3 months. FR treatment was characterized by a reduction of renal fibrosis, particularly in Unif groups. TNF-alpha protein expression was diminished in FR-treated groups.

Conclusion: This is the first evidence that FR reduced the early and long-term effect of WI in the severe ischemia model. This effect was particularly marked against fibrosis and inflammation, which would contribute to deterioration of a patient’s renal function. (J Vasc Surg 2009;49:728-40.)”
“Induction of protein disulfide isomerase (PDI) is validated as a main mechanism by which 4-hydroxybenzyl alcohol (4-HBA), an active principle of Gastrodia elata Blume, reduces cerebral infarct volumes in a murine model of focal brain ischemia/reperfusion. In contrast to its position isomers, i.e.

CD4(+) T cells from immunized wild-type, perforin-deficient, and IFN-gamma-deficient donors all initially reduced virus replication. However, prolonged viral control by IFN-gamma-competent donors suggested that IFN-gamma is important for sustained virus control. Local release

of IFN-gamma was evident by up-regulation of class II molecules on microglia in recipients of IFN-gamma producing CD4(+) T cells. CD4(+) T-cell-mediated antiviral activity correlated with diminished clinical symptoms, pathology, and demyelination. Both wild-type donor CD90.1 and recipient CD90.2 CD4(+) T cells tracked into the central nervous system (CNS) parenchyma and localized to infected white matter, correlating with decreased numbers of virus-infected oligodendrocytes in the CNS. These data support a direct,

if limited, antiviral role for CD4(+) T cells early Protein Tyrosine Kinase inhibitor during acute JHMV encephalomyelitis. Although the antiviral selleck compound effector mechanism is initially independent of IFN-gamma secretion, sustained control of CNS virus replication by CD4(+) T cells requires IFN-gamma.”
“OBJECTIVE: Mutations in the programmed cell death 10 gene, PDCD10, cause the autosomal-dominant familial cerebral cavernous malformation 3 (CCM3). Little is known about the function of this gene in disease pathogenesis.

METHODS: As a first step, we analyzed the messenger ribonucleic acid (mRNA) expression of CCM3 in the embryonic and postnatal mouse brain by in situ

hybridization. We generated and characterized CCM3-specific polyclonal antibodies and analyzed CCM3 protein expression in human cerebral and solid organ (extracerebral) tissues using immunohistochemistry.

RESULTS: In embryonic mouse brain, CCM3 mRNA is seen see more in the ventricular, subventricular, and intermediate zones, the cortical plate, the developing septum, striatum, midbrain, pons, cerebellum, and medulla. In the postnatal mouse brain, we detected CCM3/PDCD10 expression in the olfactory bulb, neocortex, striatum, septal nuclei, hippocampus, dentate gyrus, thalamic and hypothalamic nuclei, inferior colliculus, Purkinje and granule cell layers and deep nuclei of the cerebellum, and in many cells and nuclei in the medulla. Similar to CCM1 and CCM2, the CCM3/PDCD10 protein is expressed in the neurovascular unit but weakly in venous structures within cortical, subcortical, and brainstem tissue. CCM3/PDCD10 protein is strongly expressed in arterial endothelium but weakly or not at all in venous endothelium of extracerebral tissue.

CONCLUSION: The expression pattern of CCM3/PDCD10 in multiple organ systems displays similarities to CCM1 and CCM2. PDCD10/CCM3 is highly expressed in the neurovascular unit and in the arterial endothelium of structures within multiple organ systems, including the brain.

Results: Vessels stored in NaCl or PSS for >= 10 hours failed to develop tone after rewarming. Mammary arteries stored in HTK for 4 hours at 4 degrees C initially showed a well-preserved vessel function with respect to vessel tone development, as well as endothelial and smooth muscle dilatative function. However, following 4 days of cold storage, vessel tone development and dilatative responses were significantly impaired. In contrast, arteries stored in TiProtec showed full preservation MK-0518 of vessel tone as well as endothelial and smooth muscle function after 4 days of cold storage.

Even after 10 days of cold storage, endothelium-dependent relaxation was approximately 50% of control, and smooth muscle function was fully preserved. Over 2 weeks, tissue reductive capacity was significantly better maintained after cold storage in TiProtec compared with vessels stored in NaCl.

Conclusions: In contrast to traditional HTK, NaCl, JQ1 mouse or PSS storage, TiProtec solution offers an excellent potential for prolonged cold storage of human

arteries, which may close the existing gap between legal requirements for tissue banking and current cold preservation methods. (J Vasc Surg 2011;53:1063-70.)”
“Multisensory processing involving visual and auditory inputs is modulated by their relative temporal offsets. In order to assess whether multisensory integration alters the activation timing of primary visual and auditory cortices as a function of the temporal offsets between auditory and visual stimuli, a task was designed in which subjects had to judge the perceptual simultaneity of the onset of visual stimuli and brief acoustic tones. These were presented repeatedly with three different Eltanexor inter-stimulus intervals that were chosen to meet three perceptual conditions: (1) physical synchrony perceived as synchrony by subjects (SYNC); (2) physical asynchrony perceived as asynchrony (ASYNC); (3) physical asynchrony perceived ambiguously (AMB, i.e. 50% perceived as synchrony, 50% as asynchrony). Magnetoencephalographic activity was recorded during crossmodal sessions and unimodal control sessions. The activation of primary visual and

auditory cortices peaked at a longer latency for the crossmodal conditions as compared to the unimodal conditions. Moreover, the latency in the auditory cortex was longer in the SYNC than in the ASYNC condition, whereas in the visual cortex the latency in the AMB condition was longer than in the ASYNC condition. These findings suggest that multisensory processing affects temporal dynamics already in primary cortices, that such activity can differ regionally and can be sensitive to the temporal offsets of multisensory inputs. In addition, in the AMB condition the conscious awareness of asynchrony might be associated to a later activation of the primary auditory cortex. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

P2Y(1) receptor immunolabeling of Muller cells was of greater intensity following light-induced retinal degeneration, suggesting that Muller cell gliosis is accompanied by changes in P2Y(1) receptor expression. Overall, these data provide further evidence for a role of extracellular ATP in retinal signaling within subsets of retinal neurons as well as glia. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Low-frequency stimulation applied through indwelling electrodes selleckchem has been used to depress or depotentiate synaptic efficacy. Moreover it has been reported to inhibit seizure expression

and progression when started either during or after seizures. We have recently shown that low-frequency stimulation can also reduce the size of seizure-enlarged movement representations (motor maps) when delivered after 30 afterdischarges that had propagated from the hippocampus

to the neocortex. This study was designed to examine the effects of low-frequency stimulation delivered to the corpus callosum on motor map topography when applied during or after each elicited seizure. Specifically, 15 min of I Hz stimulation was applied to the corpus callosum either concurrent with or immediately following a neocortical afterdischarge that had propagated from the hippocampus. Long-Evans hooded rats were electrically stimulated twice see more daily in the right ventral hippocampus until the first neocortical afterdischarge was elicited. Rats then received low-frequency stimulation which began either with the afterdischarge or following each afterdischarge for 20 additional kindling sessions; a sham low-frequency stimulation group was also included. Afterdischarges were recorded from both hippocampal and neocortical sites, and seizure expression

was documented. One click here to six days following the last stimulation session, forelimb movement representations were derived using high-resolution intracortical microstimulation in the left sensorimotor neocortex. Low-frequency stimulation following each kindled seizure, suppressed behavioral seizure severity and hippocampal afterdischarge duration, as well as attenuated kindling-induced motor map expansion. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Transforming growth factor-beta (TGF-beta) is a potent regulatory cytokine with diverse effects on hemopoietic cells. The pivotal function of TGF-beta in the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. Among T cells, CD4(+)CD25(+)FOXP3(+) T regs contain the main source of TGF-beta that suppresses immune responses in inflammatory sites. Defects in TGF-beta 1 expression or its signaling in T cells correlate with the onset of several autoimmune diseases.