Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level-dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerstrom test of nicotine

dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited Necrostatin-1 manufacturer greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables.”
“Modulation of striatal dopamine

(DA) neurotransmission plays a fundamental role in the reinforcing and ultimately addictive 8-Bromo-cAMP manufacturer effects of nicotine. Nicotine, by desensitizing beta 2 subunit-containing Tryptophan synthase (beta 2*) nicotinic acetylcholine receptors (nAChRs) on striatal DA axons, significantly enhances

how DA is released by reward-related burst activity compared to nonreward-related tonic activity. This action provides a synaptic mechanism for nicotine to facilitate the DA-dependent reinforcement. The subfamily of beta 2*-nAChRs responsible for these potent synaptic effects could offer a molecular target for therapeutic strategies in nicotine addiction. We explored the role of alpha 6 beta 2*-nAChRs in the nucleus accumbens (NAc) and caudate-putamen (CPu) by observing action potential-dependent DA release from synapses in real-time using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in mouse striatal slices. The alpha 6-specific antagonist alpha-conotoxin-MII suppressed DA release evoked by single and low-frequency action potentials and concurrently enhanced release by high-frequency bursts in a manner similar to the beta 2*-selective antagonist dihydro-beta-erythroidine (DH beta E) in NAc, but less so in CPu. The greater role for alpha 6*-nAChRs in NAc was not due to any confounding regional difference in ACh tone since elevated ACh levels (after the acetylcholinesterase inhibitor ambenonium) had similar outcomes in NAc and CPu. Rather, there appear to be underlying differences in nAChR subtype function in NAc and CPu.

Results. After adjusting for individual-level covariates, living alone, previous postnatal depression (PND), the presence of one or more adverse life events and the 6-week EPDS score, the odds ratio (OR) for EPDS >= 12 at 6 months was 0.71 [95% confidence interval (CI) 0.53-0.97, p = 0.031]

for the intervention group (IG) women compared with the control (CAU) group women. YAP-TEAD Inhibitor 1 datasheet Two subgroups were formed by baseline severity : a ‘subthreshold’ subgroup with a 6-week EPDS score of 6-11 (n = 999) and a ‘lowest severity’ subgroup with a 6-week EPDS score of 0-5 (n = 1242). There was no difference in psychological effectiveness by subgroup (interaction term: z = -0.28, p = 0.782).

Conclusions. This study provides new evidence of a universal, enduring preventive effect for depression in women who screen negative for depression postnatally.”
“The rapid delivery of drugs of abuse to the brain is associated with an increased likelihood and severity of addiction. Here

we evaluated the hypothesis that rapidly delivered cocaine facilitates the addiction process by promoting the development of enhanced motivation for the drug. Rats lever-pressed for cocaine NU7441 mouse delivered intravenously over 5 or 90 s under fixed ratio (FR) during 6-h sessions. The motivation for cocaine was subsequently assessed using a progressive ratio (PR) schedule, where each successive drug injection cost an exponentially greater number of lever

presses, until the cessation of responding. Throughout all self-administration sessions, all rats could only take one injection every 90 s. The 5-s groups self-administered more drug than the 90-s groups across the FR sessions. Under PR, animals that had chronically self-administered rapidly delivered cocaine took more cocaine across a range of doses and regardless of whether the drug was delivered over 5 or 90 s during PR testing. The speed of delivery also determined the long-term neurobiological impact of cocaine. Fourteen days following cocaine withdrawal, caudate-putamen D2 levels were decreased only in the 90-s rats, and quinpirole-mediated G alpha(i/o)-protein activation was increased to a greater extent in the 90- vs 5-s rats. Thus, rapid delivery promotes the pursuit of cocaine in the face of rising costs and alters ifoxetine cocaine-induced changes in striatal D2 receptor number and function. As such, rapidly delivered cocaine might facilitate addiction because it more readily alters brain motivation circuits in ways that contribute to the compulsive pursuit of the drug.”
“Objectives: Hospital procedure volume has been strongly associated with postoperative mortality for a number of complex cardiovascular procedures. Although not yet described, a similar relationship might be expected for surgical procedures involving the aortic root and/or ascending aorta.

Plasma collected from up to 15 years previously was able to potently neutralize recent autologous envelopes, suggesting a lack of escape from NAb and the persistence of neutralization-sensitive

variants over time, despite significant NAb pressure. We conclude that despite the presence of broad and potent NAb responses in HIV-2-infected individuals, these are not the primary forces behind the dichotomous outcomes observed but reveal a limited capacity for adaptive selection and escape from host immunity in HIV-2 infection.”
“A single-chain Fv (scFv) fragment derived from the murine antibody IWR1 4G7, specific for human lymphocyte CD19, was engineered for stability and expression in Escherichia coli in view of future use as a therapeutic protein. We compared two orthogonal knowledge-based procedures. In one approach, we designed a mutant with 14 single amino-acid substitutions predicted

to correct destabilizing residues PLX4720 in the 4G7-wt sequence to create 4G7-mut. In the second variant, the murine CDRs were grafted to the human acceptor framework huV kappa 3-huV(H)3, with 11 additional point mutations introduced to obtain a better match between CDR graft and acceptor framework, to arrive at 4G7-graft. Compared to 4G7-wt, 4G7-mut showed greater thermodynamic stability in guanidinium chloride-induced equilibrium denaturation experiments and somewhat greater stability in human serum. The loop graft maintained the comparatively high stability of the murine loop donor, but did not improve it further. Our analysis indicates that this is due to subtle strain introduced between CDRs and framework, mitigating the otherwise highly favorable properties of the human acceptor framework. crotamiton This slight strain in the loop graft is also reflected in the binding affinities for CD19 on leukemic cells of 8.4 nM for 4G7-wt, 16.4 nM for 4G7-mut and 30.0 nM for 4G7-graft. This comparison

of knowledge-based mutation and loop-grafting-based approaches will be important, when moving molecules forward to therapeutic applications.”
“Compared with human immunodeficiency virus type 1 (HIV-1), little is known about the susceptibility of HIV-2 to antibody neutralization. We characterized the potency and breadth of neutralizing antibody (NAb) responses in 64 subjects chronically infected with HIV-2 against three primary HIV-2 strains: HIV-2(7312A), HIV-2(ST), and HIV-2(UC1). Surprisingly, we observed in a single-cycle JC53bl-13/TZM-bl virus entry assay median reciprocal 50% inhibitory concentration (IC(50)) NAb titers of 1.7 x 10(5), 2.8 x 10(4), and 3.3 x 10(4), respectively. A subset of 5 patient plasma samples tested against a larger panel of 17 HIV-2 strains where the extracellular gp160 domain was substituted into the HIV-2(7312A) proviral backbone showed potent neutralization of all but 4 viruses.

p < 0 05) In conclusion, epileptogenesis may involve hemodynamic changes that are associated with vascular reorganization during post-SE remodeling in the amygdaloid complex (C) 2010 Published by Elsevier Ireland Ltd”
“Purpose: Buccal derived graft tissue has been proven to be useful in urethral reconstruction. However, nonbuccal sources Cl-amidine chemical structure are often needed for long segment strictures or for those with prior buccal harvest. We describe a technique using full-thickness abdominal skin grafts for long segment urethroplasty and present the short-term outcomes.

Materials and Methods: A total of 21 men underwent

urethroplasty for strictures of an average of 11 cm (range 4 to 24) using abdominal wall skin. Prior urethroplasty was performed in 52% of patients and multistage repair was conducted in 48%.

Results: The recurrence rate following urethroplasty was 19%, with 9.5% requiring revision after first stage

urethroplasty. Complications included hair from the skin graft during the early part of the series (14.5%), glans dehiscence (9.5%), urethrocutaneous fistula (9.5%) and periurethral abscess (1 patient). Histological evaluation at 6 months demonstrated excellent uptake of grafts with minimal keratinization.

Conclusions: In men with significant penile scarring, lichen sclerosis and long segment urethral strictures the use of abdominal skin limits donor site morbidity, and provides a useful alternative graft source for urethroplasty when buccal mucosa or genital skin are not available Tucidinostat chemical structure or sufficient. Grafts should be harvested from nonhair bearing areas to minimize the risk of urethral hair development.”
“We previously reported the effect of a selective inducer of BiP (a MP inducer X: BIX) after permanent middle cerebral artery occlusion (MCAO) Silibinin in mice. However, in acute stroke, almost all drugs have been used clinically after the onset

of events We evaluated the effect of post-treatment of BIX after permanent MCAO in mice, and examined its neuroprotective properties in in vivo mechanism BIX (Intracerebroventricular injection at 20 mu g) administered either at 5 min or 3h after occlusion reduced both infarct volume and brain swelling, but at 6h after occlusion there was no reduction. BIX protected against the decrease in a dose-dependent manner. Furthermore. BIX reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells induced by the tschemia in ischemic penumbra. These findings indicate that post-treatment with BIX after ischemia has neuroprotective effects against acute ischemic neuronal damage in mice even when given up to 311 after MCAO BIX may therefore be a potential drug for stroke.

We thus conclude that GAG side chains of small leucine-rich proteoglycans are not a primary determinant of tensile mechanical behavior in mature rat tail tendons. (C) 2010 Elsevier Ltd. All rights reserved.”
“Long-term potentiation (LTP) of synaptic efficacy is considered a fundamental mechanism of learning and memory. At the cellular level a large

body of evidence demonstrated that the major neuromodulatory neurotransmitters dopamine (DA), norepinephrine (NE), and acetylcholine (ACh) influence LTP magnitude. Noninvasive brain stimulation protocols provide the opportunity to study LTP-like plasticity at the systems level of human cortex. Here we applied paired associative stimulation (PAS) to induce LTP-like plasticity in the primary

motor Copanlisib cortex of eight healthy subjects. In a double-blind, randomized, placebo-controlled, crossover design, the acute effects of a single oral dose of the neuromodulatory drugs cabergoline (DA agonist), haloperidol (DA antagonist), Trichostatin A methylphenidate (indirect NE agonist), prazosine (NE antagonist), tacrine (ACh agonist), and biperiden (ACh antagonist) on PAS-induced LTP-like plasticity were examined. The antagonists haloperidol, prazosine, and biperiden depressed significantly the PAS-induced LTP-like plasticity observed under placebo, whereas the agonists cabergoline, methylphenidate, and tacrine had no effect. Findings demonstrate that antagonists in major neuromodulatory neurotransmitter systems suppress LTP-like plasticity at the systems level of human cortex, in accord with evidence of their modulating action of LTP at the cellular level. This provides further supportive evidence for the known detrimental effects of these drugs on LTP-dependent mechanisms such as learning and memory. Neuropsychopharmacology (2011) 36, 1894-1902; doi:10.1038/npp.2011.75; published online 4 May 2011″
“A two-patch discrete time plant-insect model coupled through insect dispersal is studied. The model

is based on three different phases: Plant growth is followed by the dispersal of insects followed by insect attacks. Our objective is to understand how different intensities MRIP of dispersal impact both local and global population dynamics of the two-patch model. Special attention is paid to two situations: When the single-patch model (i.e., in the absence of dispersal) is permanent and when the single-patch model exhibits Allee-like effects. The existence and stability of synchronous and asynchronous dynamics between two patches is explored. If the single-patch system is permanent, the permanence of the system in two patches is destroyed by extremely large dispersals and large attacking rates of insects, thus creating multiple attractors.

Nontyphoid Salmonella was the most common responsible microorganism, and the prognosis of infection caused by Salmonella was not dismal. Outcomes of other management strategies, such as endovascular stenting, need to be compared with these results.”
“OBJECTIVE: In this study, we compare different surgical procedures regarding the functional outcome of traumatic peroneal nerve lesions.

METHODS: in a retrospective study, 48 patients with traumatic lesions (17 iatrogenic) of the peroneal nerve were evaluated. Twenty-two patients presented with lesions in continuity displaying

regenerative selleck products potential by nerve action potential recording. in these cases, surgery was restricted to either external (12x) or interfascicular neurolysis (10x). Twenty-two cases had no regenerative potential (10x) or showed discontinuity (12x) and thus were reconstructed with autologous sural nerve grafts. In four cases, a reconstructive procedure was intraoperatively abandoned as a result of the large extent of the lesion.

RESULTS: Thirty-six patients with an adequate follow-up period of at least 18 months were included in this study. Among those with external neurolysis, 73% (eight out of 11) showed a good functional outcome, obviating the need for a kick-up foot brace (M >= 4). In the interfascicular neurolysis group, 71% (five out of seven) exhibited

a similar outcome. In the grafted group, however, only 28% (five out of 18) obtained a functionally AG-14699 useful result dependent on graft length. A graft length under 6 cm(3) led to a functionally useful outcome in 44% of patients (four out of nine) compared with 11% (one out of nine) when the graft length was greater than or equal to 6 cm(3). In six patients, muscle-tendon transfers were performed, resulting

in strong, useful foot lift.

CONCLUSION: Peroneal nerve lesions lacking regenerative Lormetazepam signs should be explored. A functionally useful result (M >= 4) was achieved in 72% of the patients with either external or internal neurolysis and in 28% of the patients after a nerve graft procedure. Patients in whom nerve surgery failed to reconstitute useful foot lift need to be evaluated for their suitability to undergo a tendon transfer procedure.”
“Objective: Randomized trials have shown that endovascular repair (EVAR) of an abdominal aortic aneurysm (AAA) has a lower perioperative mortality than conventional open repair (OR). However, this initial survival advantage disappears after 1 year. To make EVAR cost-effective, patient selection should be improved. The Glasgow Aneurysm Score (GAS) estimates preoperative risk profiles that predict perioperative outcomes after OR It was recently shown to predict perioperative and long-term mortality after EVAR as well.

The Hamilton Rating Scale for Depression and the somatization subscale of the Symptom Checklist-90-Revised (SCL-90-R) were used for psychological assessment. Patients

with undifferentiated somatoform disorder had higher frequencies of the TPH1 C allele than healthy controls (p=0.02) but the difference was not significant after Bonferroni correction. The frequency of TPH1 genotype selleck chemicals llc also did not differ significantly between the patients and the healthy controls, nor did TPH2 rs1386494, 5-HTR 2A-T102C, 5-HTR 2A-G1438A or 5HTTLPR allele and genotype frequencies differ significantly between the two groups. These findings suggest that a variety of serotonin-related gene pathways are unlikely to be definite genetic risk factors for undifferentiated somatoform disorder. Therefore, the pathogenesis

of the disorder may be related to epigenetic factors, including psychosocial and cultural factors. Nonetheless, future studies need to include a larger sample of subjects and polymorphisms of more serotonin-related gene variants. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“The hepatitis B virus X protein (HBx) is essential for virus replication and has been implicated in the development of liver cancer. HBx is recruited to viral and cellular promoters and activates transcription by interacting with transcription factors and coactivators. Here, we purified HBx-associated Belnacasan purchase factors in nuclear extracts from HepG2 hepatoma cells and identified protein arginine methyltransferase 1 (PRMT1) as a novel HBx-interacting protein. We showed that PRMT1 overexpression reduced the transcription of hepatitis B virus (HBV), and this inhibition was dependent on the methyltransferase Camptothecin function of PRMT1. Conversely, depletion of PRMT1 correlated with increased HBV transcription. Using a quantitative chromatin immunoprecipitation assay, we found that PRMT1 is recruited to HBV DNA, suggesting a direct effect of PRMT1 on the regulation of HBV transcription. Finally, we showed that HBx expression

inhibited PRMT1-mediated protein methylation. Downregulation of PRMT1 activity was further observed in HBV-replicating cells in an in vivo animal model. Altogether, our results support the notion that the binding of HBx to PRMT1 might benefit viral replication by relieving the inhibitory activity of PRMT1 on HBV transcription.”
“Posttraumatic stress disorder (PTSD) is associated with intrusive trauma-related thoughts and avoidance behaviors that contribute to its severity and chronicity. This study examined thought control and avoidance coping strategies associated with both a probable diagnosis and symptom severity of combat-related PTSD in a sample of 167 treatment-seeking Operations Enduring Freedom and Iraqi Freedom (OEF-OIF) Veterans.

7% vs. 26.7% in 2008, P<.001). Of the 111 integrated applicants applying for our single position (73% of entire 2009 applicant pool), the majority of applicants were residing in the United States (88.3%) and a sizable proportion (25.2%) hid completed at least one full year of either surgical training or surgical research at an institution in the Unites States. Objective measures of academic success included mean United States Medical Licensing Examination (USMLE) Step 1

and Step 2 scores of 89.1 and 89.5, respectively. The mean number of peer-reviewed journal publications at the time of application was 2.8.

Conclusion: The number of integrated vascular surgery residency applicants far outweighs the number of available positions. Growing interest in more efficient and comprehensive vascular surgery training will continue to augment learn more demand. As educators, selleck products vascular surgeons should seize this opportunity and aggressively expand the number of available integrated residency training positions. (J Vase Surg 2009;50:1513-8.)”
“In this work we showed that nitric oxide produced via red wine- and ascorbate-dependent reduction of nitrite diffuses through the rat stomach,

inducing smooth muscle relaxation. The studies encompassed ex vivo and in vivo models of diffusion. Regarding the former, luminal (center dot)NO generated from a mixture of physiologic nitrite and ascorbate or wine diffuses across the stomach wall, being 8-20% of that produced in the mucosal side detected at high mu M range (>100 mu M) in the serosal side. In order to evaluate whether cellular dysfunction was associated with (center dot)NO diffusion at the mu M range, the gastric tissue exposed to (center dot)NO was evaluated in terms of carbachol-induced muscle contraction in fundal strips and mitochondrial respiration and showed to remain functional and metabolically active. Moreover, pre-contracted gastric strips were shown to relax 86.5 +/- 5.5% (control) and 75.0 +/- 4.0% (nitrite/ascorbate-exposed tissue) when challenged with acidified nitrite. The studies in

the living animal support the diffusion of luminal (center dot)NO to the Bumetanide gastric vasculature as, following addition of nitrite/ascorbate to rat stomach in vivo, (center dot)NO was not detected in the serosal environment but concentrations as high as 31 mu M of (center dot)NO were detected outside the stomach after cardiac arrest. Collectively, the results establish a link between the consumption of nitrite and dietary reductants (e.g., wine polyphenols) and stomach muscle relaxation via the local chemical generation of (center dot)NO. (C) 2010 Elsevier Inc. All rights reserved.”
“Four patients with high internal carotid artery (ICA) occlusive disease were indicated for surgical endarterectomy and needed additional exposure be-sides regular head rotation and extension. When indicated, in our clinic this is usually achieved by mandibular subluxation with interdental wiring.

Further, investigations showed that OECCM could increase both the mitochondrial membrane potential and the, ATP level, as well enhance the cell respiratory function. In summary, OECCM could protect ASTs from, damages induced by H2O2. Its mechanism may be related to the decrease of ROS generation and the, overloading of Ca2+, then stabilization of the

mitochondrial function. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Clostripain (CLO) produced by Clostridium histolyticum is an arginine-specific endopeptidase with the potential for applicability to diverse medical and industrial uses. In this study, we developed an expression system allowing high-level production and efficient purification of recombinant CLO (rCLO). Our expression system comprises pCLO, an rCLO expressing click here vector, and Clostridium this website perfringens 13 Delta 6, an in-frame deletion strain as to six genes encoding major virulence factors and secretory proteins. rCLO was purified from the culture supernatant of C. perfringens 13 Delta 6/pCLO by ammonium sulfate precipitation,

hydroxyapatite chromatography, and affinity chromatography on benzamidine-Sepharose. From 200 ml of culture supernatant 4.5 mg of purified rCLO was obtained. N-Terminal amino acid sequencing and molecular mass determination of the purified rCLO and commercially available CLO revealed that the two enzymes have identical subunits, a 38.1-kDa heavy chain and a 15.0-kDa light chain, indicating that rCLO is processed in the same manner as CLO. Analysis of the enzymatic activities

toward N-benzoyl-L-arginine p-nitroanilide and acyl-L-lysine p-nitroanilide showed that rCLO and CLO exhibit strict specificity for arginine at the Lactose synthase P1 position, and that the specific activity of the former is approximately 2-fold higher than that of the latter. These results indicate that the new method involving a virulence-attenuated C. perfringens strain is useful for preparing large amounts of high-grade rCLO. (C) 2010 Elsevier Inc. All rights reserved.”
“Purpose: We provide current information on the use of PSA testing for the evaluation of men at risk for prostate cancer, and the risks and benefits of early detection.

Materials and Methods: The report is a summary of the American Urological Association PSA Best Practice Policy 2009. The summary statement is based on a review of the current professional literature, clinical experience and the expert opinions of a multispecialty panel. It is intended to serve as a resource for physicians, other health care professionals, and patients. It does not establish a fixed set of guidelines, define the legal standard of care or pre-empt physician judgment in individual cases.

Results: There are two notable differences in the current policy. First, the age for obtaining a baseline PSA has been lowered to 40 years. Secondly, the current policy no longer recommends a single, threshold value of PSA, which should prompt prostate biopsy.

Only one of the six control grafts was patent, but all of the paclitaxel-coated grafts were

patent, with little neointima. The mean +/- standard error values of percentage luminal stenosis were 75.7% +/- 12.7% (control), 17.5% +/- 3.1% (low dose), and 19.7% +/- 3.0% (high dose). The values for the neointimal area (in mm(2)) were 8.77 +/- 1.66 (control), 3.53 +/- Liproxstatin-1 solubility dmso 0.73 (lose dose), and 4.24 +/- 0.99 (high dose). Compared with the control group, paclitaxel inner-coated vascular grafts significantly suppressed neointimal hyperplasia (low dose, P = .001; high dose, P = .002). Myofibroblast proliferation and migration into the graft interstices confirmed the firm attachment of the implanted graft to the surrounding tissue. Conclusions: Paclitaxel coating on the inner luminal surface of vascular grafts was effective in suppressing neointimal hyperplasia, with little inhibition of myofibroblast infiltration within the graft wall. (J Vasc Surg 2012; 55: 806-14.)

Clinical Relevance. Paclitaxel-coated vascular buy Elacridar grafts effectively inhibited the neointimal hyperplasia of hemodialysis grafts. However, paclitaxel on the outer surface of expanded polytetrafluoroethylene grafts might prevent myofibroblast proliferation, which might cause hematomas, seromas, infections, or pseudoaneurysms

in the space between the graft and surrounding tissue and result in incomplete hemodialysis needle insertion. Therefore, paclitaxel inner-coated expanded polytetrafluoroethylene grafts can reduce the coated amount of this potentially toxic drug to avoid such unwanted effects, whilst preserving its efficacy in inhibiting stenosis.”
“Spinocerebellar ataxia type 1 (SCA1) is one of a group of nine expanded CAG repeat

diseases, in which polyglutamine (polyQ) Amyloid precursor protein secretase expansion above a threshold is associated with increased disease risk and aggregation. SCA1 is unique in which the polyQ in the disease protein, ataxin1, often contains a few His residues that appear to block toxicity. Here, we ask how His insertions affect aggregation by comparing a Q(30) peptide with and without a centrally inserted His-Gln-His sequence. We found that at pH 7.5-8.5, His interruptions decrease polyQ aggregation rates but do not change the spontaneous growth mechanism: nucleated growth polymerization with a critical nucleus of one without non-fibrillar intermediates. The decreased aggregation rates are because of reductions in nucleation equilibrium constants. At pH 6, however, the His-interrupted peptide aggregates by a different mechanism that involves a low ThT-binding intermediate and produces a polymorphic amyloid product. In aggregates grown at pH 7.5, the His residues are solvent-accessible. Aggregates of His-inserted polyQ are good seeds for Q(30) elongation, suggesting the potential to recruit polyQ proteins in the cell. Our data are therefore most consistent with His insertions blocking toxicity by suppressing rates and/or altering pathways of spontaneous aggregation.