The present results are best explained within a controlled

attention view of working memory supporting the idea that object switching relies on the ability to orient the focus of attention within working memory. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“The generation of cytopathic effects by murine leukemia viruses (MLVs) in different cell types correlates with the ability of the virus to induce thymic lymphoma. We showed that the induction of apoptosis in mink epithelial cells by mink cell focus-forming (MCF) MLV infection results in the accumulation of high levels of both unintegrated viral DNA and the envelope precursor polyprotein (gPr80(env)). Comparisons this website of envelope protein expression levels of plasmid clones of the env gene of the MCF13 and noncytopathic NZB-9 MLV strains demonstrated that the accumulation of MCF13 gPr80(env) results in endoplasmic reticulum stress and is sufficient for the induction of apoptosis.”
“Our study was designed to look for interactions between fast movements and pre-existing voluntary tonic motor activity when both motor acts employ the same muscles. Five normal subjects performed a continuous sequence of two motor tasks about their right elbow joint: A tonic isometric extension (slowly increasing or decreasing) against a force transducer, followed

immediately after a “”go”" tone by a fast isotonic flexion. The position of the lower arm was recorded using a search coil system. Signals (force, position, Protein Tyrosine Kinase inhibitor and surface EMGs of triceps and biceps brachii muscles) were A/D converted and sampled at 1 kHz. A premovement silence in the tonically active triceps muscle (extensor) usually preceded

the fast flexion movement if the triceps’ tonic force was either constant or decreased slowly. If the tonic triceps activity had been increasing before the fast flexion began, this classical picture disappeared, and the premovement silence was replaced by a phasic premovement excitation. Subjects were unaware of this transient EMG and force increase in the unintended direction. Our results demonstrate unconscious reciprocal interactions between commands governing evolving movements (and tuning the motor system accordingly) and those concerned selleck chemicals with ongoing motor acts. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“The p5 promoter region of the adeno-associated virus type 2 (AAV-2) rep gene has been described as essential for Rep-mediated site-specific integration (RMSSI) of plasmid sequences in human chromosome 19. We report here that insertion of a full-length or minimal p5 element between the viral inverted terminal repeats does not significantly increase RMSSI of a recombinant AAV (rAAV) vector after infection of growth-arrested or proliferating human cells.

Possible influences on behavioral measures were tested in the elevated plus maze, spontaneous locomotor activity, and rotarod test, which are considered primarily predictive of the anxiolytic, sedative, and ataxic influence of BZs, respectively. The results confirmed the substantially diminished ataxic potential of BZ site agonists devoid of alpha(1) subunit-mediated effects,

with preserved anti-anxiety effects at 30 mg/kg of SH-053-S-CH3 and SH-053-S-CH3-2′F. However, all three ligands, dosed at 30 mg/kg, decreased spontaneous locomotor activity, suggesting that sedation may be partly dependent on activity mediated by alpha(5)-containing GABAA receptors. Hence, it could be of importance selleck compound to avoid substantial agonist activity at alpha(5) receptors by candidate anxioselective anxiolytics, if clinical sedation is to be avoided.”
“The medial preoptic area (MPOA) of the hypothalamus is critically involved in the regulation of male sexual behavior and has been implicated in several homeostatic processes. Serotonin (5-hydroxytryptamine, 5-HT) inhibits sexual behavior via effects in the MPOA, where there are high densities of 5-HT1A and 5-HT1B receptor subtypes. We used whole-cell recordings under voltage-clamp conditions to investigate the serotonergic modulation of

gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic Selleckchem AZD3965 transmission in mechanically dissociated rat MPOA neurons with native presynaptic nerve

endings. Spontaneous GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in the MPOA were completely blocked by bicuculline. Serotonin reversibly reduced the GABAergic mIPSC frequency without affecting the mean current amplitude. Serotonergic inhibition of mIPSC frequency was mimicked by (+/-)-8-hydroxy-2-dipropylaminotetralin hydrobromide, a specific 5-HT1A receptor agonist, and blocked by 1-(2- methoxyphenyl)-4-[4-(2-phthalimido)-butyl] Selleck Vorinostat piperazine hydrobromide, a specific 5-HT1A receptor antagonist. 6-Cyano-7-nitroquinoxaline-2,3-dione completely blocked spontaneous glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in the MPOA. Serotonin reversibly decreased the glutamatergic mEPSC frequency without affecting the mean current amplitude. Serotonergic inhibition of mEPSC frequency was mimicked by CGS 12066B, a specific 5-HT1B receptor agonist, and blocked by SB 216641, a specific 5-HT1B receptor antagonist. Stimulation of adenylyl cyclase with forskolin increased the frequencies of GABAergic mIPSCs and glutamatergic mEPSCs, and blocked the inhibitory effects of 5-HT. H-89, a selective protein kinase A (PKA) inhibitor, decreased the frequencies of GABAergic mIPSCs and glutamatergic mEPSCs, and blocked their reduction by 5-HT.

The patient was successfully

treated with debridement of his tongue and left carotid endarterectomy. (J Vasc Surg 2011;54:837-9.)”
“The system described here allows the expression of protein fragments into a solvent-exposed loop of a carrier protein, the beta-lactamase BlaP. When using Escherichia coli constitutive expression vectors, a positive selection of antibioresistant bacteria expressing functional hybrid beta-lactamases is achieved in the presence of beta-lactams making further screening of correctly folded and secreted hybrid RAD001 research buy beta-lactamases easier. Protease-specific recognition sites have been engineered on both sides of the beta-lactamase permissive loop in order to cleave off the exogenous protein fragment from the carrier protein by an original two-step procedure. According to our data, this approach constitutes a suitable alternative

for production of difficult to express protein domains. This work demonstrates that the use of BlaP as a carrier protein Napabucasin mouse does not alter the biochemical activity and the native disulphide bridge formation of the inserted chitin binding domain of the human macrophage chitotriosidase. We also report that the beta-lactamase activity of the hybrid protein can be used to monitor interactions between the inserted protein fragments and its ligands and to screen neutralizing molecules.”
“Introduction: Up-regulation of the type 2 cannabinoid receptor (CB2R) has been reported in (neuro)inflammatory diseases. AZD3965 In this study, we report the preclinical evaluation of [C-11]NE40 as positron emission tomography (PET) radioligand for visualization of the CB2R.

Methods: The selectivity

of NE40 for CB2R and its toxicity and mutagenicity were determined. [C-11]NE40 was evaluated by biodistribution and autoradiography studies in normal rats and a microPET study in normal mice, rats and a rhesus monkey. Specific in vivo binding of [C-11]NE40 to human CB2R (hCB(2)R) was studied in a rat model with hCB(2)R overexpression.

Results: [C-11]NE40 shows specific CB2R binding in the spleen and blood of normal rats and high brain uptake in rhesus monkey. [C-11]NE40 showed specific and reversible binding to hCB(2)R in vivo in a rat model with local hCB(2)R overexpression.

Conclusions: [C-11]NE40 shows favorable characteristics as radioligand for in vivo visualization of the CB2R and is a promising candidate for hCB(2)R PET imaging. (C) 2012 Elsevier Inc. All rights reserved.”
“We report the first documented case of distal thromboembolism originating from an abdominal aortic aneurysm (AAA) after a blunt trauma. A 72-year-old man with a known 6.2 cm AAA was brought to our emergency department with signs of bilateral acute limb ischemia developing immediately after an accidental fall.

These results suggest that anodal tDCS over the primary motor cortex enhances the precise movement of the nondominant hand for 30 min in healthy participants. NeuroReport 22: 78-82 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“The amygdaloid complex is involved in anxiety Lapatinib or fear responses to stressful stimuli. In this study the effect of neuropeptide-EI on anxiety-like behavior and its influence on adrenocortical function was tested in male Wistar rats that were injected bilaterally in the basolateral amygdala with neuropeptide-EI (1 mu g/1

mu l) or artificial cerebrospinal fluid and placed on the plus maze. The plasma corticosterone levels were analyzed in controls and plus-maze exposed animals. Neuropeptide-EI in the basolateral

amygdala significantly decreased the time spent in open arms but had no effect on locomotor activity, showing an anxiogenic effect. However, neuropeptide administration did not change serum corticosterone levels compared with vehicle controls. Our results suggest that the anxiogenic effect of neuropeptide-EI could be independent of the hypothalamic-pituitary-adrenocortical system response. NeuroReport 22: 83-87 (C) check details 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“Functional imaging studies show that motor imagery activates multiple structures in the human forebrain. We now show that phantom movements in an amputee and imagined movements in intact individuals elicit responses from neurons in several human thalamic nuclei. These include the somatic sensory nucleus receiving input from the periphery (ventral caudal), and the motor nuclei receiving input from the cerebellum [ventral intermediate (Vim)] and the basal ganglia [ventral oral posterior (Vop)]. Seven neurons the in the amputee showed phantom movement-related activity (three Vim, two Vop, and two ventral caudal). In addition, seven neurons in a group

of three controls showed motor imagery-related activity (four Vim and three Vop). These studies were performed during single neuron recording sessions in patients undergoing therapeutic treatment of phantom pain, tremor, and chronic pain conditions by thalamic stimulation. The activity of neurons in these sensory and motor nuclei, respectively, may encode the expected sensory consequences and the dynamics of planned movements. NeuroReport 22: 88-92 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“This study compared the visuospatial asymmetries in children with dyslexia and healthy children by using the manual line bisection task, and investigated the processing of spatial context with a ‘local’ cueing paradigm consisting of geometric symbols placed on the extremities of the lines.

The factors most strongly associated with return to duty were being a senior officer (adjusted OR 2.01, 95% Cl 1.71-2.35, p<0.0001), having a non-battle-related injury or disease (3.18, 2.77-3.67, p<0.0001), and presenting with chest or abdominal pain (2.48, 1.61-3.81, p<0.0001), a gastrointestinal disorder (non-surgical 2.32, 1.51-3.56, p=0.0001; surgical 2.62, 1.69-4.06, p<0.0001), or a genitourinary disorder (2.19, 1.43-3.36, p=0.0003). Covariates associated with a decreased probability of return

to duty were serving in the navy or coast guard (0.59, 0.45-0.78, p=0.0002), or marines (0.86,0.77-0.96, p=0.0083); and presenting with a combat injury (0.27, 0.17-0.44, p<0.0001), a psychiatric disorder (0.28, 0.18-0.43, buy Danusertib p<0.0001), musculoskeletal or connective tissue disorder (0.46, 0.30-0.71, p=0.0004), spinal pain (0.41, 0.26-0.63, p=0.0001), or other wound (0.54, 0.34-0.84, p=0.0069).

Interpretation Implementation of preventive measures for service members who are at highest risk of evacuation, forward-deployed treatment, and therapeutic interventions could reduce the effect of non-battle-related

injuries and disease on military readiness.”
“Background Intimate-partner violence might increase during and after Pitavastatin exposure to collective violence. We assessed whether political violence was associated with male-to-female intimate-partner violence in the occupied Palestinian territory.

Methods A nationally representative, cross-sectional survey was done between Dec 18, 2005, and Jan 18, 2006, by the Palestinian Central Bureau of Statistics. 4156 households LY294002 chemical structure were randomly selected with a multistage random cluster design, from which 3815 ever-married women aged 15-64 years were identified. We restricted our analysis to presently

married women (n=3510, 92% participation rate), who completed a short version of the revised conflict tactics scales and exposure to political violence inventory Exposure to political violence was characterised as the husband’s direct exposure, his indirect exposure via his family’s experiences, and economic effects of exposure on the household. We used adjusted multinomial logistic regression models to estimate odds ratios (ORs) for association between political violence and intimate-partner violence.

Findings Political violence was significantly related to higher odds of intimate-partner violence. ORs were 1.89 (95% CI 1.29-2.76) for physical and 2.23 (1.49-3.35) for sexual intimate. partner violence in respondents whose husbands were directly exposed to political violence compared with those whose husbands were not directly exposed. For women whose husbands were indirectly exposed, ORs were 1.61 (1.25-2.07) for physical and 1.97 (1.49-2.60) for sexual violence, compared with those whose husbands were not indirectly exposed. Economic effects of exposure were associated with increased odds of intimate-partner violence in the Gaza Strip only.

Covalent attachment of the ubiquitin-like protein side-chain NEDD8 functionally activates cullins which are common to all of these processes.

Results: The requirement for neddylation in HIV-1 and HIV-2 infectivity was tested in the presence of APOBEC3G and SAMHD1 respectively. Further the need for neddylation in HIV-1 Vpr-mediated depletion Selleck Selinexor of UNG2 was probed. Treatment with MLN4924, an adenosine sulfamate analog which hinders the NEDD8 activating enzyme NAE1, blocked neddylation of cullin4A (CUL4A). The inhibitor hindered HIV-1 infection in the presence of APOBEC3G, even when Vif was expressed, and it stopped HIV-2 infection in the presence of SAMHD1 and Vpx. Consistent with these findings,

MLN4924 prevented Vpx-mediated depletion of SAMHD1 in macrophages infected with Vpx-expressing LY3039478 HIV-2, as well as HIV-1 Vif-mediated destruction of APOBEC3G. It also stemmed Vpr-mediated UNG2 elimination from cells infected with HIV-1.

Conclusions: Neddylation plays an important role in HIV-1 and HIV-2 infection. This observation is consistent with the essential parts that cullin-based

ubiquitin ligases play in overcoming cellular anti-viral defenses.”
“Background: HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early SGC-CBP30 clinical trial viral load set point (VLSP).

Findings: Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n= 171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p< 0.001, n= 135) with nearly 1 log(10) less median viral load. Analysis of a known polymorphism at

position 97 of HLA-B showed significant associations with both lower initial viral load (p< 0.01) and lower VLSP (p< 0.05). However, this association was dependent on different amino acids at this position for each endpoint.

Conclusions: The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function.”
“Background: Testosterone deficiency is associated with insulin resistance. However, how testosterone deficiency affects insulin actions remains unclear.

In addition, we tested whether these relationships differed between older and young healthy controls. Function-structure relationships were examined in 35 first-episode patients (31 with schizophrenia, 4 with schizoaffective disorder), 54 chronic schizophrenia patients, 21 older healthy controls and 20 young healthy controls. MRI volumes of frontal Nepicastat in vitro and temporal lobe structures, as well as the whole brain, were estimated using a region-of-interest approach. Hierarchical multiple regression analyses were performed between the MRI and neuropsychological measures. Stronger relationships of immediate memory-total prefrontal cortex (PFC) volume in chronic than first-episode patients, and in older than young controls

were observed. The abstract reasoning (WCST perseverative errors)-total temporal lobe volume relationship was stronger in older than young controls. These function-structure relationships appeared unexplained by whole brain volume or age in chronic patients. A similar dissociation between young and older subjects of both healthy and patient groups suggests that a ‘bigger-is-better’ relationship style is present in older individuals regardless of a diagnosis of schizophrenia. (C) 2007 Elsevier Ireland Ltd. All rights reserved.”
“Neurodegenerative Stattic datasheet tauopathies are marked by their common pathologic feature of aggregates formed of hyperphosphorylated tau protein, which

are associated with synapse and neuronal loss. Changes in tau conformation result in both loss of normal function and gain of fibrillogenicity that leads to aggregation. Here, we discuss the pathophysiology of tau and emerging evidence of how changes in this protein might ultimately lead to neuronal death. In particular, based on recent evidence, we propose that a non-apoptotic caspase-associated form of death is occurring in tauopathy.”
“Purpose: FGFR3 mutations occur in 70%

of nonmuscle invasive bladder tumors. Although urine based FGFR3 mutation analysis can detect recurrence, its sensitivity may be limited if samples have few or no tumor cells. We determined whether test sensitivity depends selleck on tumor size and the time point of urine collection, and how to increase sensitivity.

Materials and Methods: A total of 440 urine samples from 18 patients with a suspicious bladder lesion at cystoscopy were collected during 6 days before surgery. Eight patients (300 samples) had an FGFR3 mutant tumor, including 4 each with a tumor greater than 3 and less than 1.5 cm. Polymerase chain reaction based FGFR3 analysis was done on all tumors and urine samples.

Results: FGFR3 mutations were detected in 257 of the 300 urine samples (86%) from patients with an FGFR3 mutant tumor. Assay sensitivity was 100% for tumors greater than 3 cm and 75% for tumors less than 1.5 cm. It increased to 100% in patients with a less than 1.5 cm tumor when samples were pooled during 24 hours. Sensitivity was not influenced by the time of urine collection.

RGS4 protein was not altered in short-term opiate abusers but, in long-term abusers it was significantly up-regulated (Delta = 29 +/- 6%). RGS10 protein expression was significantly decreased in short-term (Delta = -42 +/- 7%) but remained unaltered in long-term opiate abusers. RGS9 protein levels in opiate abusers did not differ from matched controls either in the short-term or in the long-term opiate abuser groups. RGS4, RGS9 and RGS10 levels were also studied in brains (frontal cortex) of rats submitted to acute and chronic morphine treatment and to spontaneous and naloxone-precipitated opiate withdrawal. Chronic

morphine treatment in rats was associated with an increase in RGS4 protein immunoreactivity (Delta = 28 +/- 7%), which persisted in spontaneous (Delta = 35 +/- 8%) and naloxone-precipitated withdrawal (Delta = 30 +/- 9%) without significant changes in RGS9 and RGS10 proteins. The specific modulation of RGS4 and RGS10 selleckchem protein expression observed in the prefrontal cortex of opiate abusers might be relevant in the neurobiology of opiate tolerance, dependence and withdrawal.

This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’. (C) 2011 Elsevier Ltd. All rights reserved.”
“Regulators of G protein signaling (RGS) proteins are important modulators of G protein-coupled receptors and, therefore, critical for cardiovascular functions. One family member, RGS5, has recently been identified

as a key regulator of vascular remodeling and pericyte maturation in tumors. Here, Fludarabine manufacturer we discuss a potential role for RGS5 and its relatives, RGS2 and 4, within the cardiovascular system. Insights into RGS5 signaling are likely to be highly significant for vascular pathologies such as hypertension, atherosclerosis, and angiogenesis. this website (Trends Cardiovasc Med 2009;19:26-30) (C) 2009, Elsevier Inc.”
“The oxidative folding of frog onconase (ONC), a member of the ribonuclease A family, was examined and shows markedly different behavior compared to its

structural homologue bovine pancreatic ribonuclease A (RNase A) under similar conditions. Application of a reduction pulse (using a small amount of reduced dithiothreitol) during the oxidative regeneration of ONC indicated the survival of the native protein along with three other (structured) species, I-1, I-2 and I-3, with the rest of the unstructured species being converted to fully reduced protein. Mass spectrometry indicates that I-1 has two disulfide bonds, whereas I-2 and I-3 have three disulfide bonds each. A disulfide mapping method, based on cyanylation, was used to identify I-2 and I-3 as des-[30-75] and des-[19-68], respectively. On enzymatic digestion using trypsin, I-1 was identified as des-[19-68, 30-75]. Differences in the intermediates that are generated during the oxidative folding of the two structural homologues, RNase A and ONC, demonstrate that regenerative pathways are not necessarily influenced by tertiary structure.

Conclusions:

Radical prostatectomy as salvage is feasible for men in whom high intensity focused ultrasound failed, https://www.selleckchem.com/products/lonafarnib-sch66336.html but with a higher morbidity than for primary surgery. Pathology results are alarming given the number of cases with extraprostatic extension yet early followup data suggest acceptable oncologic control. These results should be factored in when counseling men who wish to undergo primary high intensity focused ultrasound.”
“Sleep loss strongly affects brain function and may even predispose susceptible individuals to psychiatric disorders. Since a recurrent lack of sleep frequently occurs during adolescence, it has been implicated in the rise in depression

incidence during this particular period of life. selleck One mechanism through which sleep loss may contribute to depressive symptomatology is by affecting hippocampal function. In this study, we examined the effects of sleep loss on hippocampal integrity at young age by subjecting adolescent male rats to chronic sleep restriction (SR) for 1 month from postnatal day 30 to 61. They were placed in slowly rotating drums for 20 h per day and were allowed 4 h of rest per day at the beginning of the light phase. Anxiety was measured using an open field and elevated plus maze test, while saccharine preference was used as an indication of anhedonia. All tests were performed after 1 and 4 weeks of SR. We further studied effects of SR on hypothalamic-pituitary-adrenal (HPA) axis activity, and at the end of the experiment, brains were collected to measure hippocampal volume and neurogenesis. Behavior of the SR animals was not affected, except for a transient suppression of saccharine preference after 1 week of SR. Hippocampal volume was significantly reduced in SR rats compared to home cage

and forced activity controls. This volume reduction was not paralleled by reduced levels of hippocampal neurogenesis and could neither be explained by elevated levels of glucocorticoids. PD0325901 Thus, our results indicate that insufficient sleep may be a causal factor in the reductions of hippocampal volume that have been reported in human sleep disorders and mood disorders. Since changes in HPA activity or neurogenesis are not causally implicated, sleep disturbance may affect hippocampal volume by other, possibly more direct mechanisms. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: Long-term prostate cancer specific mortality after radical prostatectomy is poorly defined in the era of widespread screening. An understanding of the treated natural history of screen detected cancers and the pathological risk factors for prostate cancer specific mortality are needed for treatment decision making.

Patients were directed to continuously adjust head orientation and to maintain the stimulus pattern at the center of the array. Postural tasks that present progressive difficulties were given during the use of the device. Pre- and post-treatment distribution of the sensory organization test (SOT) composite score showed an average value of 38.3 +/- 8.7 and 59.9 +/- 11.3, respectively, indicating a statistically significant improvement (p = 0.01). Electrotactile tongue biofeedback significantly improved the postural control of the study group, even if they had not improved with conventional VR. The electrotactile tongue biofeedback system was able to supply additional information about head position with respect to gravitational

vertical orientation in the absence of vestibular input, improving postural control. Patients with BVL can integrate electrotactile information in their postural Rabusertib order control in order click here to improve stability after conventional VR. These results were obtained and verified not only by the subjective questionnaire but also by the

SOT composite score. The limitations of the study are the small sample size and short duration of the follow-up. The current findings show that the sensory substitution mediated by electrotactile tongue biofeedback may contribute to the improved balance experienced by these patients compared to VR. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Emerging evidence suggests that the neuroprotective effects of valproic acid (VPA) occur via inhibition of histone deacetylases (HDACs) and activation of gene expression. This study assessed the ability of four VPA derivatives to cause histone hyperacetylation and protect against glutamate-induced excitotoxicity in cultured neurons. We found that PF299804 manufacturer (S)-2-pentyl-4-pentynoic acid (compound III) and (+/-)-2-hexyl-4-pentynoic acid (compound V) were far more potent and robust than VPA in inducing histone hyperacetylation and protecting against glutamate excitotoxicity. Thus, the increase in histone acetylation elicited by compounds III and V was significant at 5 mu M and reached a maximal increase of 600-700% at 50-100 mu M, compared with only a 200% increase by VPA

at 100 mu M. The neuroprotective effects of compounds III and V were evident at 10-25 mu M and reached a complete protection at 50-100 mu M, while a significant partial protection by VPA was observed at 100 mu M. These two compounds were also more effective than VPA in increasing HSP70-1a and HSP70-1b mRNA levels. At 50 mu M, compound V was most robust in increasing HSP-1a mRNA levels, followed by compound III, and then by VPA. HSP-1b mRNA was only significantly upregulated by compounds V and III, but not by VPA or other VPA derivatives under these treatment conditions. Our results suggest that these two VPA derivatives may ultimately be developed into potent neuroprotective drugs in preclinical and clinical studies. Published by Elsevier Ireland Ltd.