For the total sample, baseline employment status and sustained at

For the total sample, baseline employment status and sustained attention predicted employment status at follow-up. For those employed at baseline, better sustained attention, higher global functioning, more positive symptoms and less alcohol use predicted persistent employment at follow-up. For those unemployed at baseline, none of the variables predicted change in employment status. Implications of these results are discussed. RepSox nmr (C) 2011 Elsevier Ireland

Ltd. All rights reserved.”
“Associations among maltreatment and traumatic experiences in childhood and adolescence, later substance use, and subsequent mental health outcomes for individuals with schizophrenia-spectrum disorders have been initially explored in previous studies; however, research on these factors in socially disadvantaged patients with first-episode psychosis is unavailable. This exploratory, correlational analysis examined associations between maltreatment and trauma-related variables (e.g., traumatic experiences, parental harsh discipline, violence exposure) and: social variables (years of education attained and extent of Axis IV psychosocial problems at initial hospitalization), substance abuse (age at

initiation of alcohol and cannabis use, as well as estimates of lifetime intake of both), and positive and negative symptom severity. Rates of childhood abuse and traumatic events were remarkably high in the sample. Years of educational attainment and number of Axis IV psychosocial problems were substantially correlated with several domains of childhood abuse/traumatic events. Age at initiation of alcohol and cannabis use, and lifetime alcohol and cannabis intake, were correlated AZD5363 concentration with a number of trauma domains. Whereas positive symptom severity was correlated with four of the trauma variables, negative symptom severity was correlated only with prior emotional neglect. These results provide insights into the relations among childhood traumatic events, substance use. and clinical features of first-episode psychosis, creating hypotheses for future research. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Memory

impairment is Resveratrol often associated with depression. However, the literature is not uniform whether such impairment constitutes state and/or trait characteristics. One-hundred-and-twelve clinically depressed (CDs), previously depressed (PDs), and never depressed (NDs) subjects (T2 diagnostic status),were assessed with the California Verbal Learning Test (CVLT) at T1 and re-assessed 9 years later with the revised version, CVLT-II. At T1 no deficit in verbal memory between CDs and PDs compared to NDs was found, in which the majority of the subjects were younger adults. At follow-up the majority of CDs and PDs had suffered one or several recurrent depressive episodes. Repeated-measures analysis of variance showed, in particular and irrespective of group, a significant decline in recall measures over time.

Results from early model communities showed that increased comple

Results from early model communities showed that increased complexity is associated with decreased local stability. I demonstrate that increasing both the number of species in a community and the connectance between these

species results in S63845 an increased probability of local stability in discrete-time competitive communities, when some species would show unstable dynamics in the absence of competition. This is shown analytically for a simple case and across a wider range Of community sizes using simulations, where individual species have dynamics that call range from stable point equilibria to periodic or more complex. Increasing the number of competitive links in the community reduces per-capita growth rates through an increase in competitive feedback, stabilising oscillating dynamics. This result was robust to the introduction of a trade-off between competitive ability and intrinsic growth rate and changes in species interaction strengths. This throws new light on the discrepancy between the theoretical view that increased complexity reduces Stability and the empirical view that more complex systems are more likely to be stable, giving one explanation for the relative lack of complex dynamics found in natural systems. I examine how these results

relate to diversity-biomass stability relationships and show that an analytical Solution derived CBL0137 in vivo in the region of stable equilibrium dynamics captures many features of the change in biomass fluctuations With community size in Communities including species with oscillating dynamics. (C) 2009 Elsevier Ltd. All rights reserved.”
“ADAMs are transmembrane proteins implicated in several biological functions, including cytokine and growth factor shedding, fertilization, muscle and nervous system development. Here, we show for the first time that ADAM23, which is predominantly expressed in the central nervous system, co-localizes with cellular prion protein (PrP(C)) at plasma membrane of mouse hippocampal

neurons and neuroblastoma cells. Co-immunoprecipitation and pull-down assay showed a physical selleck chemicals llc interaction between ADAM23 and both recombinant and endogenous PrP(C). Glycosylation seems to be not relevant to the observed interaction since both ADAM23 and PrP(C) recombinant proteins expressed in bacteria or extracted from eukaryotic cells treated with tunicamycin are still able to bind each other. In vitro binding assays also suggested that the disintegrin domain of ADAM23 is able to interact directly with PrP(C). Taken together, these findings point out PrP(C) as a novel molecular partner for ADAM23 in the nervous systems. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“beta-Amyloid peptide (A beta), the primary protein component in senile plaques associated with Alzheimer’s disease (AD), has been implicated in neurotoxicity associated with AD.

However, the vaccine did not protect vaccinated animals from peni

However, the vaccine did not protect vaccinated animals from penile SIV challenge. At the lowest SIV exposure dose (10(3) 50% tissue culture infective doses), 2 of 9 Ad5-seropositive animals immunized with the Ad5 SIV vaccine became infected compared to 0 of 34 animals infected in the other animal

groups (naive animals, Ad5-seropositive animals immunized with the empty Ad5 vector, Ad5-seronegative animals immunized with the Ad5 SIV vaccine, and Ad5-seronegative animals immunized with the empty Ad5 vector). Penile exposure to more concentrated virus inocula buy Capmatinib produced similar rates of infection in all animal groups. Although setpoint viral loads were unaffected in Step vaccinees, the Ad5 SLY-immunized animals had significantly lower acute-phase plasma vRNA levels GDC-941 compared to unimmunized animals. Thus, the results of the nonhuman primate (NHP) study described here recapitulate the lack of protection against HIV acquisition seen in the Step Trial and suggest a greater risk of infection in the Ad5-seropositive animals immunized with the Ad5 SLY vaccine. Further studies are necessary to confirm

the enhancement of virus acquisition and to discern associated mechanisms.”
“We suggest that working memory (WM) performance can be conceptualized as the interplay of low-level feature binding processes and top-down control, relating to posterior and frontal brain regions and their interaction in a distributed neural network. We propose that due to age-differential trajectories of posterior and frontal brain regions top-down control processes are not fully mature until young adulthood and show marked decline with advancing age, whereas binding processes are relatively mature in children, but show senescent

decline in older adults. A review of the literature spanning from middle childhood to old age shows that binding and top-down control processes undergo profound changes across the lifespan. We illustrate commonalities and dissimilarities between children, younger adults, and older adults reflecting the change in the two components’ relative contribution Carnitine palmitoyltransferase II to visual WM performance across the lifespan using results from our own lab. We conclude that an integrated account of visual WM lifespan changes combining research from behavioral neuroscience and cognitive psychology of child development as well as aging research opens avenues to advance our understanding of cognition in general. (C) 2012 Elsevier Ltd. All rights reserved.”
“It is known that respiratory syncytial virus (RSV) is the main cause of bronchiolitis and pneumonia in young children. RSV infection often leads to severe acute lung immunopathology, but the underlying immune mechanisms are not yet fully elucidated.

HepG2 cells were treated with three different concentrations of B

HepG2 cells were treated with three different concentrations of BBP (0, 10, or 25 M) for 24 or 48 h. Following incubation, the cells were subjected to proteomic analysis using two different pI ranges (4-7 and 6-9) and large-size two-dimensional gel electrophoresis. Results showed resolution of a total of 2776 protein spots. Of these, 29, including 19 upregulated and 10 downregulated proteins, were identified by electrospray ionization-mass spectrometry-mass spectrometry (ESI-MS/MS). Among these, the identities of cystatin C, Rho guanine nucleotide dissociation inhibitor, gelsolin, DEK protein, Raf kinase inhibitory

protein, triose phosphate isomerase, heptaglobin-related protein, inter-alpha-trypsin inhibitor heavy chain H2, and electron transfer flavoprotein subunit LY2874455 beta were confirmed by Western blot analysis. These proteins were found to be involved in apoptosis, signaling, selleck screening library tumor progression, energy metabolism, and

cell structure and motility. Therefore, these proteins have potential to be employed as biomarkers of BBP exposure and may be useful in understanding mechanisms underlying the adverse effects of BBP.”
“BACKGROUND

Few data are available on the long-term outcome of endovascular repair of abdominal aortic aneurysm as compared with open repair.

METHODS

From 1999 through 2004 at 37 hospitals in the United Kingdom, we randomly assigned 1252 patients with large abdominal aortic aneurysms (>= 5.5 cm in diameter) to undergo either endovascular or open repair; 626 patients were assigned to each group. Patients were

followed for rates of death, graft-related complications, reinterventions, and resource use until the end of 2009. Logistic regression and Cox regression were used to compare outcomes in the two groups.

RESULTS

The 30-day operative mortality was 1.8% in the endovascular-repair Morin Hydrate group and 4.3% in the open-repair group (adjusted odds ratio for endovascular repair as compared with open repair, 0.39; 95% confidence interval [CI], 0.18 to 0.87; P=0.02). The endovascular-repair group had an early benefit with respect to aneurysm-related mortality, but the benefit was lost by the end of the study, at least partially because of fatal endo-graft ruptures (adjusted hazard ratio, 0.92; 95% CI, 0.57 to 1.49; P=0.73). By the end of follow-up, there was no significant difference between the two groups in the rate of death from any cause (adjusted hazard ratio, 1.03; 95% CI, 0.86 to 1.23; P=0.72). The rates of graft-related complications and reinterventions were higher with endovascular repair, and new complications occurred up to 8 years after randomization, contributing to higher overall costs.

CONCLUSIONS

In this large, randomized trial, endovascular repair of abdominal aortic aneurysm was associated with a significantly lower operative mortality than open surgical repair.

(C) 2008 IBRO Published by Elsevier Ltd All rights reserved “

(C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: We evaluated the incidence of cryptorchidism and inguinal hernias in patients with posterior urethral valves, and compared characteristics in patients with and without cryptorchidism AP26113 purchase or inguinal hernia.

Materials and Methods: A total of 200 patients with posterior urethral valves treated

between 1953 and 2003 were identified from a hospital database. Patient records were retrospectively reviewed. The state of testicular descent and the presence of inguinal hernias were recorded in 192 patients. Patient characteristics were analyzed.

Results: Of 192 patients 31 (16%) had cryptorchidism, which was bilateral in 9 (29%). A total of 21 patients (11%) had inguinal hernias that were not associated with cryptorchid testes. The patients with cryptorchidism, and to some extent the patients with hernias, appeared to have a more severe form of posterior urethral valves than those without cryptorchidism. At the time of diagnosis the median serum creatinine concentration was 100 mu mol/l (range 38

to 460) in boys with cryptorchidism and 87 (14 to 593) in boys without cryptorchidism (p = 0.131). At 6-month followup the median serum creatinine levels were 90 mu mol/l (range 31 to 573) in patients with cryptorchidism and 45 (19 to 504) in patients without cryptorchidism (p = 0.006). Cryptorchidism was also more common CH5424802 price in cases

diagnosed neonatally compared to those diagnosed at a later age (14 of 52 patients, 27% vs 14 of 112, 12.5%, respectively, p = 0.027).

Conclusions: The incidence of cryptorchidism and inguinal hernias requiring surgery is high in patients with posterior urethral valves. Patients with cryptorchidism appear to have a more severe form not of posterior urethral valves than those with normal testes.”
“The etiology of idiopathic Parkinson’s disease is thought to involve interplay between environmental factors and predisposing genetic traits, although the identification of genetic risk factors remain elusive. The neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP) produces parkinsonian-like symptoms and pathology in mice and humans. As sensitivity to MPTP is genetically determined in mice this provides an opportunity to identify genes and biological mechanisms that modify the response to an exogenous agent that produces a Parkinson’s disease-like condition. MPTP primarily targets dopaminergic nerve terminals in the striatum and elicits changes in striatal gene expression. Therefore, we used Affymetrix(R) and qRT-PCR technology to characterize temporal mRNA changes in striatum in response to MPTP in genetically MPTP-sensitive, C57BL/6J, and MPTP-resistant Swiss Webster and BCL2-associated X protein (Bax)-/- mice. We identified three phases of mRNA expression changes composed of largely distinct gene sets.

This technique was employed in the current study to examine the r

This technique was employed in the current study to examine the roles of the uvula in BP regulation during postural alterations

in anesthetized rats. Enhanced Natronomonas pharaonis halorhodopsin (eNpHR), a light-driven chloride ion pump, was selectively expressed in uvular PCs using a lentiviral vector containing the PC-specific L7 promoter. The eNpHR-expressing PCs were then illuminated by orange laser (593 nm) either during 30 degrees head-up or 30 degrees head-down tilts. The eNpHR-mediated photoinhibition of the uvula attenuated the extent of BP recovery after a BP increase induced by postural changes during head-down tilts. By contrast, photoinhibition had no statistically significant effect on BP recovery during head-up tilts. The effects of photoinhibition on BP during selleck products tilts were significantly different from those observed

during the resting condition, indicating that cerebellar control of BP during tilts is dynamic rather than static. Taken together, these results suggest that PCs in the uvula dynamically regulates BP maintenance during postural PD0325901 alterations. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Human serum butyrylcholinesterase (Hu BChE) is the most viable candidate for the prophylactic treatment of organophosphate poisoning. A dose of 200 mg/70 kg is predicted to protect humans against Phosphatidylinositol diacylglycerol-lyase 2 x LD(50) of soman. Therefore, the aim of this study was to develop procedures for the purification of gram quantities of this enzyme from outdated human plasma or Cohn Fraction IV-4. The purification of Hu BChE was accomplished by batch adsorption on procainamide-Sepharose-CL-4B affinity gel followed by ion-exchange chromatography on a DEAE-Sepharose column. For the purification

of enzyme from Cohn Fraction IV-4, it was resuspended in 25 mM sodium phosphate buffer, pH 8.0, and fat was removed by decantation, prior to batch adsorption on procainamide-Sepharose gel. In both cases, the procainamide gel was thoroughly washed with 25 mM sodium phosphate buffer, pH 8.0, containing 0.05 M NaCl, and the enzyme was eluted with the same buffer containing 0.1 M procainamide. The enzyme was dialyzed and the pH was adjusted to 4.0 before loading on the DEAE column equilibrated in sodium acetate buffer, pH 4.0. The column was thoroughly washed with 25 mM sodium phosphate buffer, pH 8.0 containing 0.05 M NaCl before elution with a gradient of 0.05-0.2 M NaCl in the same buffer. The purity of the enzyme following these steps ranged from 20% to 40%. The purity of the enzyme increased to > 90% by chromatography on an analytical procainamide affinity column. Results show that Cohn Fraction IV-4 is a much better source than plasma for the large-scale isolation of purified Hu BChE. Published by Elsevier Inc.

Comorbidities, fracture characteristics, and treatment details we

Comorbidities, fracture characteristics, and treatment details were recorded; BYL719 in vitro primary outcomes were 30-day mortality and complication rates; secondary outcomes were length of hospital stay and long-term survival.

RESULTS: Surgically treated patients tended to have more severe fractures with larger displacement. Charlson comorbidity scores were similar in both groups. Thirty-day mortality was 3.6% in the surgical group and 7.1% in the nonsurgical group, and the 30-day complication rates were 17.9% and 25.0%, respectively; these differences were not statistically significant.

Surgical patients had significantly longer lengths of hospital stay than nonsurgical patients (11.8 days vs 4.4 days). Long-term AZD5153 research buy median survival was not significantly different between groups.

CONCLUSION: The 30-day mortality and complication rates in surgically and nonsurgically

treated patients were comparable. Elderly patients faced relatively high morbidity and mortality regardless of treatment modality; thus, age alone does not appear to be a contraindication to surgical fixation of C2 fractures.”
“Purpose: Endovascular aneurysm repair (EVAR) is associated with high graft-related complication rates during follow-up. Anatomical fit between patient and endograft could be an important factor for successful treatment. Aim was to assess whether extent of thrombus, calcification, angulation, and tortuosity are associated with occurrence of complications after EVAR.

Materials and methods: Patients in either United Kingdom EVAR trial 1 or 2 were included if they had undergone EVAR within 6 months of randomization and had a preoperative computed tomography (CT) scan of adequate quality in the core laboratory. Three-dimensional CT Janus kinase (JAK) imaging was used to assess extent of preoperative thrombus, calcification, angulation, and tortuosity in aneurysm neck and iliac segments. Cox regression modeling, adjusted for the variables tested and for known confounding variables, was used to investigate whether these factors were associated with increased rates of reported

first complications.

Results: A total of 217 patients with 53 first graft-related complications were analyzed after a mean follow-up of 3.6 years. Adjusted hazard ratios (95% confidence intervals, P values) for complications per unit increase of variable were 0.96 (0.92-0.99, 0.018) for neck thrombus, 1.06 (1.00-1.12, 0.044) for neck calcification, 1.02 (1.00-1.05, 0.079) for neck angulation, 1.04 (1.01-1.06, 0.011) for common iliac thrombus, 0.96 (0.93-1.00, 0.033) for common iliac calcification, and 5.96 (1.53-23.28, 0.010) for common iliac tortuosity.

Conclusion: Increased neck angulation and calcification and common iliac thrombus and tortuosity are associated with higher rates of graft-related complications after EVAR. Increased neck thrombus and common iliac calcification appear to protect against complications.

(C) 2009 IBRO Published by Elsevier Ltd All rights reserved “

(C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Neurodegeneration and signs of immune activation, with T cell infiltration, major histocompatibility complex class II expression and glial activation, occur in many neurological diseases. Although particular qualities of the inflammatory response have been proposed to be of importance, still very little is known about the exact factors

that determine susceptibility Silmitasertib to neurodegeneration. Mechanistic studies have yielded conflicting results, where inflammation is suggested both to attenuate and aggravate loss of nerve cells depending on the circumstances. In this context experimental genetic dissection in relevant rodent models such as experimental autoimmune see more encephalomyelitis and mechanical nerve injury can be a valuable tool to identify important genes/molecules/pathways.

We here review emerging evidence using this approach that indicates different pathways related both to adaptive and local innate immune responses, which determine strain-specific susceptibility to neuroimmune inflammation and neurodegeneration. Exact positioning of genes in these types of complex traits will be important for the understanding of pathogenetic mechanisms and to direct the focus of functional studies using classical experimental tools. Ultimately, a better knowledge about the Carteolol HCl interplay

between the nervous system and the local and systemic immune system can define new ways of intervention in neurodegenerative processes. (C) 2009 Published by Elsevier Ltd on behalf of IBRO.”
“Inflammation plays a central role in the pathophysiology of numerous disorders of the nervous system, but is also pivotal for repair processes like peripheral nerve regeneration. In this review we summarize recent advances in cellular magnetic resonance imaging (MRI) while nuclear imaging methods to visualize neuroinflammation are covered by Wunder et al. [Wunder A, Klohs J, Dirnagl U (2009) Noninvasive imaging of central nervous system inflammation with nuclear and optical imaging. Neuroscience, in press]. Use of iron oxide-contrast agents allows assessment of inflammatory processes in living organisms. Upon systemic application, circulating small (SPIO) and ultrasmall particles of iron oxide (USPIO) are preferentially phagocytosed by monocytes before clearance within the reticuloendothelial system of the liver, spleen and lymph nodes.

Sarcopenia was defined in two ways: ALM/height

Sarcopenia was defined in two ways: ALM/height AZD5363 chemical structure squared (ALM/ht(2)) and ALM adjusted for height and FM (residuals). Sarcopenic-obesity categories (referent, obese, sarcopenic,

and sarcopenic-obese) were defined by cross-classifying ALM/ht(2) and obesity (% body fat: more than 30 for men and more than 40 for women). Mobility limitation was defined as self-reported inability to walk one-half mile, climb stairs, or perform heavy housework. Sex-specific logistic regression calculated odds ratios (OR) and 95% confidence intervals (Cl) for mobility limitation, adjusting for covariates.

Results. Sixteen percent of men and 30% of women had mobility limitation. Among men, both ALM/ht(2) (OR = 6.3, 95% Cl = 2.5-16.1) and residuals (OR = 4.6, 95% Cl = 2.0-10.5) sarcopenia were associated with increased limitation. For sarcopenic-obesity, odds of limitation was higher in sarcopenic (OR = 6.1, 95% Cl = 2.2-16.9) and sarcopenic-obese categories (OR = 3.5, 95% CI = 1.0-12.7) but suggested no synergistic effect. In women, only residuals sarcopenia was associated with higher odds of limitation (OR = 1.8, 95% Cl = 1.2-2.9).

Conclusions. Low lean mass is associated with mobility limitations after

accounting for body size and fat, and lean and FM have independent effects on mobility in elders. These findings support selleck chemicals llc previous reports that sarcopenia definitions should consider body size and fat.”
“Hormones and neurobiological factors may be regulated differently in suicidal versus non-suicidal depressive patients. There is currently limited knowledge about the relation of substances in the Renin-Angiotensin-Aldosterone system to depression and suicidality. We therefore investigated whether plasma levels

of renin and aldosterone differ between suicide attempters, non-suicidal depressive patients and healthy controls. Furthermore, we analyzed the relation of renin and aldosterone to psychiatric symptoms in the patients. Suicidal patients with MDD, adjustment disorder and dysthymia, as well as two control groups Protirelin consisting of non-suicidal MDD patients and healthy subjects, were rated using the Comprehensive Psychopathological Rating Scale (CPRS), including the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Plasma samples were frozen immediately after collection and stored at -80 degrees C for 5-18 years. Aldosterone and renin levels were analyzed using radioactive- and chemiluminescent immunoassays. We found that suicide attempters with MDD had significantly lower plasma levels of aldosterone than the other patient groups, as well as than the healthy controls. Moreover, increasing severity of psychiatric symptoms was associated with lower aldosterone levels in the suicide attempters with MDD.

The level of 27-hydroxycholesterol was elevated in 1 year old ani

The level of 27-hydroxycholesterol was elevated in 1 year old animals for all APOE genotypes. Interestingly, lathosterol an indicator of cholesterol synthesis was significantly reduced in the 1 year old learn more animals for all APOE genotypes. APOE epsilon 4 expressing mice exhibited statistically lower levels of lathosterol compared to APOE epsilon 2 in both the young and old mice. Oxidized cholesterol metabolites were significantly lower in APOE epsilon 2 mice compared to other genotypes at 8 weeks old. Although minimal differences were observed between APOE epsilon 3 and epsilon 4 knock-in (KI) mice, these findings

indicate that there are some clear APOE genotype specific effects on brain cholesterol synthesis and associated metabolic pathways, particularly in APOE epsilon 2 KI mice. (C) 2010 KU55933 order IBRO. Published by Elsevier Ltd. All rights reserved.”
“Focused ultrasound-induced opening of the blood-brain barrier (BBB) in the presence of ultrasound contrast agents is a promising strategy for a targeted drug delivery to the brain. The aim of our study was to identify whether brain molecular stress pathways are targeted by ultrasound treatment. Using an upper level of

acoustic pressures in combination with microbubbles, which have been previously reported as reliable for BBB opening without causing tissue damage, we found that ultrasound leads to an increased ubiquitinylation of proteins in neuronal (11 +/- 3 ubiquitin-overexpressing cells per optical field) but not glial cells 6 h post-insonation, increasing to 16 (+/- 4) labelled cells after 24 h. No changes in the expression of Hsp70 and Hsc70 were detected over 24 h. Ultrasound treatment was followed by limited apoptosis after 24 h (32 +/- 6 cleaved-caspase Vildagliptin 3-positive cells per optical field) in the insonated areas. Only neurons were identified in the apoptotic population. Although these observations may not be applicable for all acoustic parameters useful

for BBB opening, they demonstrate that insonation of the rat brain with the parameters used in our experiments is a useful tool for BBB opening and induces specific cellular stress response restricted to neuronal cells. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Previous studies have shown that the Wistar-Kyoto (WKY) rat strain is more sensitive to stressors and consumes significant quantities of alcohol under basal as well as stressful conditions when compared to other strains. Given that the glutamate neurotransmitter system has been implicated in depression and addiction, the goals of the present study were to investigate the effects of stress and stress-alcohol interactions on N-methyl-D-aspartate (NMDA) receptors in the rat brain. Thus this study measured the binding of [(3)H] MK-801 to NMDA receptors in the prefrontal cortex (PFC), caudate putamen (CPu), nucleus accumbens (NAc), hippocampus (HIP) and basolateral amygdala (BLA) in WKY rats in comparison to the Wistar (WIS) rat strain.