Ten out of

the twelve sponge species studied showed activ

Ten out of

the twelve sponge species studied showed activity in one or more of the bioassays. Aqueous 4 extracts of Cinachyrella sp. and Petromica citrina showed a large action spectrum over resistant-bacteria such as Staphylococcus aureus, coagulase-negative staphylococci and Enterococcus faecalis. Aqueous extract of P. citrina was fractioned and aqueous fraction showed a greatest inhibitory activity on Staphylococcus strains. In addition, this fraction demonstrated a bactericidal effect on exponentially growing S. aureus cells at the MIC (16 mu g/mL). The mechanism of action of bioactive fraction is still unclear, but we showed that it affect protein biosynthesis of Staphylococcus. Our results demonstrated for the first time selleck compound that P. citrina is a potential source of new selleck chemicals drugs for the treatment of infections by antibiotic-resistant bacteria.”
“Glutamate receptors are important target molecules of the acute effect of ethanol. We studied ethanol sensitivity of homomeric GluR-D receptors expressed in human embryonic kidney 293 cells and examined whether recently discovered transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor regulatory proteins (TARPs) affect ethanol sensitivity. Coexpression of the TARPs, stargazin, and gamma 4 increased

the time constant (tau-value) of current decay in the presence of agonist, thus slowing the onset of desensitization and increasing the steady-state current. Ethanol produced less inhibition of the peak current than the steady-state current for all types of the GluR-D receptors. In addition, ethanol concentration-dependently accelerated the rate of desensitization, measured as the tau-value of fast decay of peak current. This effect was enhanced with coexpression of TARPs. The recovery from desensitization was

slowed down Selleck Proteasome inhibitor by coexpression of gamma 4 but ethanol did not affect this process in any GluR-D combination. The results support the idea that increased desensitization is an important mechanism in the ethanol inhibition of AMPA receptors and indicate that coexpression of TARPs can alter this effect of ethanol. (C) 2009 Elsevier Inc. All rights reserved.”
“Introduction: Large villous adenomas or adenocarcinomas of the rectum can determine secretory diarrhea, associated with a depleting syndrome of prerenal acute renal failure, hyponatremia, hypokalemia, and hypoproteinemia, with favorable prognosis if early detected and properly treated. The syndrome is rare, with approximately 50 cases reported in the literature. Aim: Acute renal failure, caused by fluids and electrolytes hypersecretion, secondary to a malignant rectal villous adenoma is revealed in a 55-year-old patient, admitted with major hydro-electrolytic and acid-base disturbances to our Nephrology Department.

Several possible surgical approaches were considered, including a

Several possible surgical approaches were considered, including a transsylvian approach and a contralateral interhemispheric approach. Roscovitine Ultimately, the patient underwent a contralateral interhemispheric

trans-striatocapsular approach to the lesion and was discharged without neurologic deficit within 72 hours.\n\nCONCLUSION: The approach described here is a novel alternative to transsylvian or supracarotid approaches to the 432 anterior inferior basal ganglia and in this patient provided a well-tolerated surgical corridor that allowed complete resection of his cavernoma. We discuss several advantages and disadvantages of the various approaches to the anterior inferior basal ganglia.”
“Early lymphocyte recovery following auto-SCT for non-Hodgkin’s lymphoma (NHL) has been reported to be associated with improved outcome. The significance of early lymphocyte recovery following a stem cell transplant in NHL

subtype diffuse large B-cell lymphoma (DLBCL) in the rituximab era remains unclear. Patients who underwent an auto-SCT at our institution for DLBCL during the time period 1998-2008 (n=115) SN-38 in vivo were included in the study. Patient characteristics were well-balanced in both rituximab naive and rituximab-exposed groups. Prior rituximab therapy did not affect lymphocyte recovery on day 14 or day 28. Lymphocyte recovery on day 14 and day 28 and prior rituximab had no impact on survival after auto-SCT for DLBCL, despite early benefit. Other factors such as age, stage at presentation, number of salvage

regimens, mobilization procedure, conditioning regimen, pre-transplant radiation therapy and pre-transplant disease status had no impact on survival. Our data showed that the survival benefit with early lymphocyte recovery and prior rituximab seen in previous reports may be lost with longer follow-up. Prior rituximab therapy does not appear to influence the lymphocyte count at days 14 and 28 following auto-SCT. Our findings suggest that future trials should consider manipulating the immune system as a post transplant intervention to improve long-term outcome. Bone Marrow Transplantation (2012) 47, 82-87; doi: 10.1038/bmt.2011.29; published MK-0518 online 28 February 2011″
“Secondary hyperparathyroidism (SHPT) may contribute to the systemic illness that accompanies chronic heart failure (CHF). Healthy elderly with vitamin D deficiency who did not develop hyperparathyroidism (functional hypoparathyroidism, FHPT) had lower mortality than those who did. This study was designed to examine determinants of the PTH response in the vitamin D insufficient CHF patients. Sixty five vitamin D insufficient males with NYHA class II and III and 20 control subjects age >= 55 years were recruited. Echocardiography, physical performance, NT-pro-BNP, PTH, 25-hydroxyvitamin D (25(OH) D), adiponectin and bone activity surrogate markers (OPG, RANKL, OC, beta-CTx) were assessed.

Twenty percent of the patients needed ureteral dilation, and 15%

Twenty percent of the patients needed ureteral dilation, and 15% of the patients had a ureteral access sheath placed intraoperatively. The overall complication rate was 2.6% (major = 0.7%, minor = 1.9%). Complications included: Four urinary tract infections,

two patients with urosepsis, and one patient with urinary 3 retention. No patients had ureteral perforation or ureteral avulsion.\n\nConclusions: Using the ureteroscope as the safety mechanism, ureteroscopy is safe with regard to maintaining renal access and control. Routine safety wires during ureteronephroscopy are not necessary assuring the ureteroscope is in the kidney.”
“This article provides a comprehensive review of rheumatologic considerations for a clinician when evaluating a patient with neck pain. Clearly, anatomic derangements of the cervical spine should be considered when a patient complains of cervicalgia. However, one ISRIB ic50 must also entertain the possibility of a systemic illness as the cause of the pain. Examples of diseases that may present with a prominent feature of neck pain are discussed, including rheumatoid arthritis, ankylosing spondylitis, diffuse idiopathic skeletal hyperostosis, myositis, and fibromyalgia. Evidence of an underlying rheumatic illness may guide the clinician in a different therapeutic direction.”
“Background: The aim of this study is to verify the effects of the

combined and classic training of different isometric rates Epigenetics inhibitor of force development (RFD) parameters of legs. Materials and Methods: Three groups of female athletes was tested: Experimental group (N = 12), classically trained group (N = 11), and control

group (N = 20) of athletes. The isometric “standing leg extension” and “Rise on Toes” tests were conducted to evaluate the maximal force, time necessary time to reach it and the RFD analyzed at 100 ms, 180 ms, 250 ms from the onset, and 50-100% of its maximal result. Results: The maximal RFD of legs Selleck AZD6738 and calves are dominant explosive parameters. Special training enhanced the RFD of calves of GROUP(SPEC) at 100 ms (P = 0.05), at 180 ms (P = 0.039), at 250 ms (P = 0.039), at 50% of the F-max (P = 0.031) and the F-max (P = 0.05). Domination of GROUP(SPEC) toward GROUP(CLASS) and GROUP(CONTROL) is in case of legs at 100 ms (P = 0.04); at 180 ms (P = 0.04); at 250 ms (P = 0.00); at 50% of the F-max (P = 0.01) and at the F-max (P = 0.00); in case of calves at 100 ms (P = 0.07); 180 ms (P = 0.001); at 250 ms (P = 0.00); at 50% of the F-max (P = 0.00) and at F-max (P = 0.000). Conclusion: Dominant explosive factors are maximal RFD of leg extensors and calves, and legs at 250ms. Specific training enhanced explosiveness of calves of GROUP(SPEC) general and partial domination of GROUP(SPEC) by 87% over GROUP(CLASS), and 35% over GROUP(CONTROL).”
“Statement of problem. The development of computer-aided design/computer-aided manufacturing technology has enabled the fabrication of implant-retained restorations.

Our findings suggest cautious optimism that the slowdown in the g

Our findings suggest cautious optimism that the slowdown in the growth of health spending may persist-a change that, if borne out, could have a major impact on US health spending projections and fiscal challenges facing the country.”
“Background: Surfaces in congregate settings, such as vehicles used for mass transportation, can become contaminated with infectious microorganisms and facilitate disease transmission. We disinfected surfaces contaminated with H1N1 influenza viruses using hydrogen peroxide (HP) vapor at concentrations below 100 ppm and triethylene glycol (TEG)-saturated air containing 2 ppm of TEG at 25 degrees C.\n\nMethods Influenza

viruses in aqueous suspensions were deposited on stainless-steel coupons, allowed to dry at ambient conditions, and then exposed for https://www.selleckchem.com/products/ch5424802.html up to 15 minutes to 10 to 90 ppm of HP vapor or

TEG-saturated air. Virus assays were done on the solution used to wash the viruses Ruboxistaurin supplier from these coupons and from coupons treated similarly but without exposure to HP or TEG vapor.\n\nResults: After 2.5 minutes, exposure to 10-ppm HP vapor resulted in 99% inactivation. For air saturated with TEG at 25 to 29 degrees C, the disinfection rate was about 1.3 log(10) reductions per hour, about 16 times faster than the measured natural inactivation rate under ambient conditions.\n\nConclusions: Vapor concentrations of 10 ppm HP or 2 ppm TEG can provide effective surface disinfection. At these low concentrations, the potential for damage to even the avionics of an airplane would be expected to be minimal. At a TEG vapor concentration of 2 ppm, there are essentially no health risks to people.”
“There exist very few results on mixing for non-stationary processes. However, mixing is often required in statistical inference selleck chemicals llc for non-stationary processes such as time-varying ARCH (tvARCH) models. In this paper, bounds for the mixing rates of a stochastic process are derived in terms of the conditional densities

of the process. These bounds are used to obtain the alpha, 2-mixing and beta-mixing rates of the non-stationary time-varying ARCH(p) process and ARCH(infinity) process. It is shown that the mixing rate of the time-varying ARCH(p) process is geometric, whereas the bound on the mixing rate of the ARCH(infinity) process depends on the rate of decay of the ARCH(infinity) parameters. We note that the methodology given in this paper is applicable to other processes.”
“Identification of appropriate donor cell types is important for lung cell therapy and for lung regeneration. Previous studies have indicated that mesenchymal stromal cells derived from human bone marrow (hBM-MSCs) and from human adipose tissue (hAT-MSCs) may have the ability to trans-differentiate into lung epithelial cells. However, these data remain controversial.

Forty-two patients achieving complete hematological remission wer

Forty-two patients achieving complete hematological remission were assessed for minimal residual disease (MRD) by WT1 gene expression; 34 by flow-cytometry (flow-MRD). Patients CA4P who were flow-MRD negative had a better 3-year disease-free (DFS; 79.5% vs. 27.3%; p =.032) compared with patients who were still positive after induction. Interestingly, DFS of flow-MRD positive patients

was not related to the amount of flow-detected clone population (>= or < 1%, p =.41) but to WT1 reduction (Delta WT1, 3-year DFS; 46.2% vs. 0% if Delta WT1

was >= or < of 1.5 log, p =.001). In AML, combining MRD results provided by WT1 quantification and flow-cytometry improves the reliability of MRD-based prognostic HSP990 mw stratification. Similar analyses by further larger studies should be advocated. (C) 2013 Elsevier Ltd. All rights reserved.”
“The objective of the present study was to investigate the in vitro and in vivo hepatoprotective properties of Cichorium endivia L. extract (CEE), and to identify its chemical constituents. CEE significantly blocked JQ1 the oxidative stress and cytotoxicity induced by tert-butyl hydroperoxide (t-BHP) in HepG2 cells. Meanwhile, oral administration of CEE to mice before the treatment of t-BHP exhibited a markedly protective effect by lowering serum levels of ALT and AST, inhibiting the changes in liver biochemistry including MDA, SOD, GSH and GST, as well

as ameliorating the liver injuries according to the histopathological observations. According to the acute oral toxicity test, the LD(50) of CEE was greater than 5,000 mg/kg, which demonstrates that the CEE can be considered practically non-toxic. Phytochemical analysis of CEE showed the presence of five compounds identified as 2-furanmethanol-(5′-> 11)-1,3-cyclopentadiene-[5,4-c]-1H-cinnoline, which is a new cinnoline derivative derived from a natural source but not synthesis, 2-phenylethyl-beta-D-glucopyranoside, kaempferol-3-O-beta-D-glucoside, kaempferol, and adenosine. In the ORAC assay, CEE and its constituents kaempferol and kaempferol-3-O-beta-D-glucoside had considerable antioxidant potency.

Self-sustaining, dense populations of naturalized Kangaroo Paws o

Self-sustaining, dense populations of naturalized Kangaroo Paws occur at several localities and are highly attractive to local nectar-feeding birds. The populations show high levels of seed set with or without bird pollination. Given the known propensity of Kangaroo Paws to hybridise in their native range in Australia, and confusion about the species identity of naturalized populations in South Africa, it was essential to resolve some key taxonomic issues in the group. We constructed the first molecular phylogeny for all species

of the Kangaroo Paw group (genera Anigozanthos and Macropidia; family Haemodoraceae). As previously determined by taxonomists working on herbarium specimens, naturalized populations were identified Rabusertib mw as A. flavidus. In addition, we also identified a second species, A. rufus. Relative genome size estimates for Anigozanthos species indicated that small inter-specific differences in genome sizes are positively correlated to hybrid fitness. Anigozanthos flavidus and A. rufus have relatively ‘compatible’ genomes and may produce fertile hybrids under field conditions. However, for species whose genome size differ more

than similar to 30%, there is little inter-specific selleck chemicals llc compatibility and consequently a very low risk of producing fertile hybrids. In conclusion, we recommend that trade in Kangaroo Paws in South Africa should be temporarily restricted and that particular cultivars should first be subjected to a careful risk assessment.”
“Grapevine leafroll-associated virus-7 (GLRaV-7) was transmitted from, all Albanian grapevine accession to Tetragonia

expansa check details by the parasitic dodder Cuscuta reflexa and to Nicotiana occidentalis by Cuscuta europea. Cuscuta campestris was infected by GLRaV-7 but could not transfer the virus to an experimental host, Transmission of the verified by reverse transcription-polymerase chain reaction (RT-PCR) from total nucleic acid (TNA) and double-stranded RNA (dsRNA) extracts front all five plain species. DsRNA extractions separated on agarose gels showed strong visible bands corresponding to high-molecular-weight virus genome and to sub-genomic RNA. GLRaV-7 was maintained in C. reflexa C. campestris, T. expansa, and N. occidentalis for more than 4 years. Infected T. expansa and the Cuscuta species remained symptom-less while N. occidentalis showed severe symptoms leading to stunting and decline of the plants. Quantitative PCR showed great differences in the titer of GLRaV-7 between the tissues of its, natural and experimental host plants. This is the first report oil a Virus of the Closteroviridae that was successfully transmitted to an herbaceous plant by dodder. Virus replication could be demonstrated in Cuscuta. Both the new experimental hosts of GLRaV-7 and Cuscuta followed extraction of dsRNA for further characterization of the viral genome, which previously required grapevine scraping of phloem.

Real-time PCR conducted with RNA samples from individual rats fed

Real-time PCR conducted with RNA samples from individual rats fed varying amounts of quercetin together with the microarray analysis showed that quercetin caused marked dose-dependent increases in the mRNA expression of Gsta3, Gstp1, and Gstt3. Some moderate increases were also noted in the mRNA expression of isoenzymes belonging to the Gstm class. Quercetin selleck compound also dose-dependently increased the mRNA expression of Akr1b8 and Akr7a3. However, it did not affect

the parameters of the other Gst and Akr isoenzymes. It is apparent that quercetin increases the mRNA expression of Gst and Akr involved in drug metabolism in an isoenzyme-specific manner. Inasmuch as Gst and Akr isoenzymes up-regulated in their gene expression are involved in the prevention and attenuation of cancer development, this consequence may account for the chemopreventive propensity of quercetin.”
“Electronegative low-density lipoprotein (LDL(-)) is a minor modified LDL subfraction that is present in blood. LDL(-) promotes inflammation and is associated with the development of atherosclerosis. We previously reported that the increase of cytokine release promoted by this lipoprotein subfraction in monocytes is counteracted by high-density lipoprotein (HDL). HDL also inhibits a phospholipase C-like activity (PLC-like) intrinsic

to Savolitinib clinical trial LDL(-). The aim of this work was to assess whether the inhibition of the PLC-like activity by HDL could decrease the content of ceramide (CER) and diacylglycerol (DAG) generated in LDL(-). This knowledge would allow

us to establish a relationship between these compounds and the inflammatory activity of LDL(-). LDL(-) incubated at 37 degrees C for 20 h increased its PLC-like activity and, subsequently, the amount of CER and DAG. We found that incubating LDL(-) with HDL decreased both products in LDL(-). Native check details LDL was modified by lipolysis with PLC or by incubation with CER-enriched or DAG-enriched liposomes. The increase of CER in native LDL significantly increased cytokine release, whereas the enrichment in DAG did not show these inflammatory properties. These data point to CER, a resultant product of the PLC-like activity, as a major determinant of the inflammatory activity induced by LDL(-) in monocytes.”
“Plumbogummite PbAl3(PO4)(2)(OH,H2O)(6) is a mineral of environmental significance and is a member of the alunite-jarosite supergroup. The molecular structure of the mineral has been investigated by Raman spectroscopy. The spectra of different plumbogummite specimens differ although there are many common features. The Raman spectra prove the spectral profile consisting of overlapping bands and shoulders.


“Objective-To determine the association among signalment,


“Objective-To determine the association among signalment, health status, other clinical variables, and treatments and events during cardiopulmonary cerebral resuscitation (CPCR) with the return of spontaneous circulation (ROSC) for animals with cardiopulmonary arrest (CPA) in a veterinary teaching hospital.\n\nDesign-Cross-sectional study.\n\nAnimals-161 dogs and 43 cats with CPA.\n\nProcedures-Data were gathered GSI-IX during a 60-month period on animals that had CPA and underwent CPCR. Logistic regression was used to evaluate effects of multiple predictors for ROSC.\n\nResults-56 (35%) dogs and 19 (44%) cats had successful CPCR. Twelve (6%) animals (9 dogs and 3 cats) were discharged

from the hospital. Successfully resuscitated dogs were significantly more likely to have been treated with mannitol, lidocaine, fluids, dopamine, corticosteroids,

or vasopressin; had CPA while anesthetized; received chest compressions while positioned in lateral recumbency; and had a suspected cause of CPA other than hemorrhage or anemia, shock, hypoxemia, multiple organ dysfunction syndrome, cerebral trauma, malignant arrhythmia, or an anaphylactoid reaction and were less likely to have been treated with multiple doses of epinephrine, had a longer duration of CPA, or had multiple disease conditions, VX-661 order compared with findings in dogs that were not successfully resuscitated. Successfully resuscitated cats were significantly more likely to have had more people participate in CPCR and less likely to have had shock as the suspected cause of CPA, compared with findings in AL3818 cell line cats that were not successfully resuscitated.\n\nConclusions and Clinical Relevance-The prognosis was grave for animals with CPA, except for those that had CPA while anesthetized. (J Am Vet Med Assoc 2009;235:50-57)”
“Darier disease (DD) is an autosomal dominant skin disease. Treatment is often difficult and unsatisfactory because of the chronic nature of the condition

and the irritant potential of various therapeutic agents. Systemic vitamin A derivatives such as acitretin and isotretinoin are the treatment of choice, but their use is often limited by class-specific side-effects. Alitretinoin (9-cis-retinoic acid), has antiproliferative and anti-inflammatory potential, and is licensed for the systemic treatment of chronic hand eczema in a number of countries. Unlike acitretin, alitrenoin requires contraception in women of childbearing age to be extended for only 1month after the end of treatment. There is evidence that alitretinoin might be a well-tolerated alternative for the systemic treatment of various retinoid-responsive skin diseases. We present two cases of women with refractory DD successfully treated with alitretinoin without marked side-effects, who both obtained near-complete remission of their skin lesions.”
“Over the last several decades, researchers have achieved remarkable progress in the field of organometallic chemistry.


“Background Idiopathic granulomatous mastitis (IGM) is a


“Background. Idiopathic granulomatous mastitis (IGM) is a benign breast disease that has been described as a rare granulomatous inflammation (GI). It can mimic inflammatory breast cancer. Material and methods. We included women with a diagnosis of IGM referred to an oncologic hospital between January 01, 2007 and to March 31, 2011, with diagnosis of breast cancer, in whom biopsy reported GI, without other cause related. The aim of this study was to review the clinical, radiologic and pathologic characteristics BLZ945 solubility dmso of a cohort of women with IGM. Results. We analyzed 58 patients; mean age was 38 12 years. Mammography showed diffuse asymmetry (n = 19) and focal asymmetry (n = 13); breast

ultrasound showed heterogeneous and hypoechoic areas (n = 28) and lumps (n = 21) as the most frequent lesions.

All biopsies showed lobulocentric GI. Treatment included antibiotics (n = 20), steroids (n = 8), both treatments (n = 20), surgical excision Sulfobutylether-β-Cyclodextrin (n = 3) and observation (n = 7). Forty-three patients (74%) had complete remission; mean time to remission was 9.5 +/- 5.8 months. Fifteen (26%) had partial remission. Any patient had progression or relapse. Conclusions. IGM is a benign breast condition that may mimic breast inflammatory cancer. Ultrasonography and mammography findings reveal characteristic data that can be useful for establishing the diagnosis; however, biopsy is the gold standard for its diagnosis and should be taken in any patient even with a mild suspicion of cancer.”
“Low to moderate doses of vasopressin have been used in the treatment of cathecholamine-dependent vasodilatory shock in sepsis or after cardiac surgery. We evaluated the effects of vasopressin on jejunal mucosal perfusion, gastric-arterial pCO(2) gradient and the global splanchnic oxygen demand/supply relationship in patients with vasodilatory shock after cardiac surgery.\n\nEight mechanically

ventilated patients, dependent on norepinephrine to maintain mean selleck inhibitor arterial pressure (MAP) >= 60 mmHg because of septic/post-cardiotomy vasodilatory shock and multiple organ failure after cardiac surgery, were included. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h for 30-min periods. Norepinephrine was simultaneously decreased to maintain MAP at 75 mmHg. At each infusion rate of vasopressin, data on systemic hemodynamics, jejunal mucosal perfusion, jejunal mucosal hematocrit and red blood cell velocity (laser Doppler flowmetry) as well as gastric-arterial pCO(2) gradient (gastric tonometry) and splanchnic oxygen and lactate extraction (hepatic vein catheter) were obtained.\n\nThe cardiac index, stroke volume index and systemic oxygen delivery decreased and systemic vascular resistance and systemic oxygen extraction increased significantly, while the heart rate or global oxygen consumption did not change with increasing vasopressin dose.


“How do biological agents plan and organise a smooth accur


“How do biological agents plan and organise a smooth accurate path to shift from one smooth mode of behaviour to another as part of graceful movement that is both plastic and controlled? This paper addresses the question in conducting a novel shape analysis of approach and adjustment phases in rapid voluntary target aiming and 2-D reaching hand actions. A number of mode changing experiments are reported that investigate these actions under a range of goals and conditions.

After a typically roughly aimed approach, regular projective adjustment is observed that has height and velocity kinematic profiles that are scaled copies of one another. This empirical property is encapsulated as a novel LDK378 concentration self-similar shift function. The mathematics shows that the biological shifts consist of continual deviation from their full Taylor series everywhere throughout their mTOR inhibitor therapy interval, which is a deep form of plasticity not described before. The experimental results find the same approach and adjustment strategy to occur with behavioural trajectories over the full and varied range of tested goals and conditions. The trajectory shapes have

a large degree of predictability through using the shift function to handle extensive variation in the trajectories’ adjustment across individual behaviours and subjects. We provide connections between the behavioural features and results and various neural studies to show how the methodology may be exploited. The conclusion is that a roughly aimed approach followed by a specific highly

plastic shift adjustment can provide a regular basis for fast and accurate goal-directed motion in a simple and generalisable way.”
“Although the proapoptotic BH3-only protein, Bim, is required for deletion of autoreactive thymocytes, Bim-deficient mice do not succumb to extensive organ-specific autoimmune disease. To determine whether other BH3-only proteins safeguard tolerance in the absence of Bim, we screened mice lacking Bim as well as other BH3-only proteins. Most strains showed no additional defects; however, mice deficient for both Puma and Bim spontaneously developed autoimmunity in multiple Cytoskeletal Signaling inhibitor organs, and their T cells could transfer organ-specific autoimmunity. Puma- and Bim-double-deficient mice had a striking accumulation of mature, single-positive thymocytes, suggesting an additional defect in thymic deletion was the basis for disease. Transgenic mouse models of thymocyte deletion by peripheral neoantigens confirmed that the loss of Bim and Puma allowed increased numbers of autoreactive thymocytes to escape deletion. Our data show that Puma cooperates with Bim to impose a thymic-deletion checkpoint to peripheral self-antigens and cement the notion that defects in apoptosis alone are sufficient to cause autoimmune disease.