TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies.

The lifetime prevalence of panic disorder (PD) is up to 4% worldwide and there is substantial evidence that genetic factors contribute to the development of PD. Single-nucleotide polymorphisms (SNPs) in TMEM132D, identified in a whole-genome association study (GWAS), were found to be associated with PD in three independent samples, with a two-SNP haplotype associated in each of three samples in the same direction, and with a P-value of 1.2e-7 in the combined sample (909 cases and 915 controls). Independent SNPs in this gene were also associated with the severity of anxiety symptoms in patients affected by PD or panic attacks as well as in patients suffering from unipolar depression. Risk genotypes for PD were associated with higher TMEM132D mRNA expression levels in the frontal cortex. In parallel, using a mouse model of extremes in trait anxiety, we could further show that anxiety-related behavior was positively correlated with Tmem132d mRNA expression in the anterior cingulate cortex, central to the processing of anxiety/fear-related stimuli, and that in this animal model a Tmem132d SNP is associated with anxiety-related behavior in an F2 panel. TMEM132D may thus be an important new candidate gene for PD as well as more generally for anxiety-related behavior.

Renopathological Microstructure Visualization from Formalin Fixed Kidney Tissue by Matrix-Assisted Laser/Desorption Ionization-Time-of-Flight Mass Spectrometry Imaging.

Understanding early stage renal malfunctions with regard to the glomerular filtration processes is essential for nephropathological prescreening strategies and intervention at an early stage. Mass spectrometry imaging (MSI) in combination with histopathology can provide an universal analytical approach. Proteomic and lipidomic aspects of glomerular biocompositions were applied for micro-structural differentiation in healthy rat kidney samples. Usability of commonly used tissue embedding media and the compatibility of histological staining and fixation methods were of interest. It was demonstrated that ultra-thin tissue samples (500 nm, 1 and 10 µm) can be used for lipid and peptide-based differentiation at the glomerular resolution level in formalin-fixed tissue samples in combination with preceding histological staining for correlating optical and molecular mass images.

Acute stress regulation of neuroplasticity genes in mouse hippocampus CA3 area--possible novel signalling pathways.

Stress exposure can lead to the precipitation of psychiatric disorders in susceptible individuals, but the molecular underpinnings are incompletely understood. We used forced swimming in mice to reveal stress-regulated genes in the CA3 area of the hippocampus. To determine changes in the transcriptional profile 4 h and 8 h after stress exposure microarrays were used in the two mouse strains C57BL/6J and DBA/2J, which are known for their differential stress response. We discovered a surprisingly distinct set of regulated genes for each strain and followed selected ones by in situ hybridisation. Our results support the concept of a phased transcriptional reaction to stress. Moreover, we suggest novel stress-elicited pathways, which comprise a number of genes involved in the regulation of neuronal plasticity. Furthermore, we focused in particular on dihydropyrimidinase like 2, to which we provide evidence for its regulation by NeuroD, an important factor for neuronal activity-dependent dendritic morphogenesis.

Tumor promotion by the peroxisome proliferator nafenopin involving a specific subtype of altered foci in rat liver.

The involvement of tumor promotion in the hepatocarcinogenic action of peroxisome proliferators has not been generally accepted. We studied the effect of nafenopin (NAF) as a model compound in a two-stage initiation-promotion protocol. Carcinogenesis was initiated by a single dose of aflatoxin B1 (AFB1) in female (AFB1, 5 mg/kg) and male (AFB1, 2 mg/kg) Wistar rats. After recovery NAF was fed via the diet, providing a daily dose of 100 mg/kg body weight. Phenobarbital (PB) (50 mg/kg body weight) was fed to female rats as a positive control. The following results were obtained. (a) At weeks 40, 55, 59, and 70, significantly more and larger liver tumors were present in AFB1-NAF-treated rats than in rats receiving either compound alone, and the effect of the combined treatment was clearly more than additive, in three independent experiments including both sexes. This suggests tumor promotion by NAF. Male rats responded more strongly than females. Similarly, PB enhanced the yield of liver tumors. Histologically, tumors were hepatocellular adenoma or carcinoma. In group AFB1-PB the majority consisted of eosinophilic and glycogenstoring cells. However, adenoma and carcinoma of groups AFB1-NAF and O-NAF consisted of weakly basophilic cells. (b) Phenotypically altered foci were evaluated in hematoxylin- and eosin-stained liver sections from the female rats. NAF treatment after AFB1 had little effect on number and size of eosinophilic-clear cell foci and decreased the number of trigroid foci. However, it led to a dramatic increase (20-fold after 70 weeks of NAF treatment) in number and size of foci of a special phenotype that was extremely rare after AFB1 alone and virtually absent in group AFB1-PB. Hepatocytes in these foci are characterized by weak diffuse basophilia and some eosinophilia, similar to the phenotype in adenoma and carcinoma, and by absence of gamma-glutamyltranspeptidase (GGT) expression. Based on these findings, we propose the hypothesis that NAF promotes the development of liver tumors via a mechanism involving amplification of a specific subtype of altered hepatic foci.

Infrequent mutations of the p53 gene in pulmonary carcinoid tumors.

Archival specimens of 25 pulmonary carcinoids including 15 cases of typical carcinoid, 9 atypical carcinoids, and 1 large-cell neuroendocrine carcinoma were analyzed for mutations in exons 5 to 8 of the p53 gene. Mutations were identified in 4 tumors, including 3 out of 15 (20%) typical carcinoids and the single large-cell neuroendocrine carcinoma, but none of the atypical carcinomas showed a mutation. The mutations were acquired during tumor development since they were not present in the corresponding nontumorous tissue. All mutations in the typical carcinoids, a tumor type without epidemiological link to cigarette smoking, were G to A transitions. The level of p53 protein was investigated by immunohistochemistry with the polyclonal antibody CM-1. None of the pulmonary carcinoids investigated showed a positive reaction, despite the presence of missense mutations in two cases. Negative staining of carcinoids with mutations was also observed with the monoclonal antibodies pAb1801 and DO-1. Our data suggest that point mutations of the p53 gene are infrequent in pulmonary carcinoids thus contrasting the findings in other histological types of lung cancer, in particular small-cell lung cancer. Moreover, negative immunostaining for p53 is no indicator for the absence of p53 missense mutations in typical carcinoids.

Presupplementary motor area activation during sequence learning reflects visuo-motor association.

In preceding studies (Hikosaka et al., 1996; Sakai et al., 1998) we have shown that the presupplementary motor area (pre-SMA), an anterior part of the medial premotor cortex, is active during visuo-motor sequence learning. However, the paradigm required the subjects first to acquire correct visuo-motor association and then to acquire correct sequence, and it was still unknown which of the two processes the pre-SMA is involved in. To further characterize the role of pre-SMA, we have conducted another series of functional magnetic resonance imaging experiments using three learning paradigms. The three were the same in that they involved a visuo-motor association component, but they differed in terms of the involvement of sequential components; one involved no sequence learning, whereas the other two involved learning of motor sequence or perceptual sequence. Comparison of the learning conditions with the any-order button press condition revealed pre-SMA activation in all three paradigms. The pre-SMA activation remained unchanged during learning of visuo-motor associations but decreased during learning of sequences, suggesting that the pre-SMA is related to visuo-motor association rather than sequence. The decrease of pre-SMA activation in the sequential paradigms may reflect the process by which individual visuo-motor associations were replaced by the formation of sequential procedural memory, which occurs outside the pre-SMA. Thus activation of the pre-SMA was related to the extent to which the task performance depended on conscious visuo-motor associations.

PCR-based assays for the detection of monoclonality in non-Hodgkin's lymphoma: application to formalin-fixed, paraffin-embedded tissue and decalcified bone marrow samples.

In crucial cases the diagnosis of non-Hodgkin's lymphoma (NHL) still represents a challenge to the pathologist since morphological criteria do not always help to distinguish between reactive and malignant lymphoproliferations. Clonality assays are a useful supplement since monoclonal cell proliferation is strong evidence for malignancy. The polymerase chain reaction (PCR) can be utilized to establish the clonal origin of B- or T-cell lymphocyte populations by amplification of rearranged immunoglobulin and T-cell receptor (TCR) genes. In the present study DNA was isolated from a variety of neoplastic and nonneoplastic formalin-fixed, paraffin-embedded lymph nodes (n = 62), cutaneous tissue (n = 9), samples of miscellaneous origin (n = 11), and reported here for the first time, decalcified bone marrow samples (n = 35). These samples were submitted to PCR-based assays directed against the immunoglobulin heavy-chain (IgH), immunoglobulin kappa light-chain (IgL kappa), and TCR gamma chain genes. The impact of various decalcifying agents on the ability to amplify DNA was investigated by PCR-based amplification of a single copy gene. Buffered and nonbuffered EDTA was found not to impede amplification of DNA fragments up to 300 bp in length. In lymph node and cutaneous specimens monoclonality was detected in 83% of B-NHL cases using a seminested PCR approach for the amplification of IgH, whereas the same approach gave rise to monoclonal bands in 80% of bone marrow samples. The subsequent amplification of IgL kappa helped to raise the sensitivity of detection to 94%. Monoclonality was detected in seven of nine T-cell NHLs by amplification of TCR gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

RNA expression profiling in depressed patients suggests retinoid-related orphan receptor alpha as a biomarker for antidepressant response.

Response to antidepressant treatment is highly variable with some patients responding within a few weeks, whereas others have to wait for months until the onset of clinical effects. Gene expression profiling may be a tool to identify markers of antidepressant treatment response and new potential drug targets. In a first step, we selected 12 male, age- and severity-matched pairs of remitters and nonresponders, and analyzed expression profiles in peripheral blood at admission and after 2 and 5 weeks of treatment using Illumina expression arrays. We identified 127 transcripts significantly associated with treatment response with a minimal P-value of 9.41 × 10(-)(4) (false discovery rate-corrected). Analysis of selected transcripts in an independent replication sample of 142 depressed inpatients confirmed that lower expression of retinoid-related orphan receptor alpha (RORa, P=6.23 × 10(-4)), germinal center expressed transcript 2 (GCET2, P=2.08 × 10(-2)) and chitinase 3-like protein 2 (CHI3L2, P=4.45 × 10(-2)) on admission were associated with beneficial treatment response. In addition, leukocyte-specific protein 1 (LSP1) significantly decreased after 5 weeks of treatment in responders (P=2.91 × 10(-2)). Additional genetic, in vivo stress responsitivity data and murine gene expression findings corroborate our finding of RORa as a transcriptional marker of antidepressant response. In summary, using a genome-wide transcriptomics approach and subsequent validation studies, we identified several transcripts including the circadian gene transcript RORa that may serve as biomarkers indicating antidepressant treatment response.

Monoclonality of intraepidermal T lymphocytes in early mycosis fungoides detected by molecular analysis after laser-beam-based microdissection.

The identification of neoplastic lymphocytes in early lesions of mycosis fungoides is difficult because of the scarcity of the infiltrate and the presence of reactive T lymphocytes admixed with neoplastic cells. Molecular analysis of the T cell receptor gene rearrangement using the polymerase chain reaction technique demonstrates monoclonality only in a proportion of these cases. The exact location of the malignant clone is unknown, and at present it is not clear whether neoplastic cells in early lesions reside within the epidermis, the superficial dermis, or both. We analyzed skin lesions from five patients with early mycosis fungoides using the polymerase chain reaction technique after microdissection of the specimens. In each case the epidermis was separated from the dermis using a laser-beam microdissection technique. Three samples were prepared from each lesion: one containing only the epidermis, one only the superficial dermis, and one the entire specimen. A distinct band could be observed in the epidermal sample in four cases, indicating the presence of an intraepidermal monoclonal population of T lymphocytes. The dermal sample revealed a monoclonal pattern in two cases (both of them showing clonality also within the epidermis). Analysis of the entire specimen revealed a monoclonal pattern only in two cases. Our results demonstrate that intraepidermal lymphocytes in early mycosis fungoides often show a monoclonal pattern of T cell receptor gene rearrangement. Microdissection of biopsy specimens may enhance the sensitivity of the polymerase chain reaction technique.

Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study.

BACKGROUND: Functional imaging studies suggest a specific role of the anterior brain regions in the pathogenesis of major depression. The aim of this study was to evaluate possible neurochemical alterations in the frontomesial cortex in patients with major depressive episode using in vivo proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: Single voxel (1)H-MRS was performed in 19 patients with major depressive episodes and 18 age-matched healthy controls within the anterior cingulate cortex and the parietal white matter. Absolute concentrations were estimated for N-acetyl-aspartate, choline-containing compounds, total creatine, myo-inositol, unresolved glutamate and glutamine (Glx) and glutamate alone (Glu). Voxel composition was analyzed by image segmentation into cerebrospinal fluid (CSF), grey and white matter. RESULTS: MANOVA test for Glx and Glu using age, percent CSF and percent grey matter contribution as covariates yielded a significant group effect within the anterior cingulate due to decrease of Glx in patients (-10.4%, p =.013). Considering only severely depressed patients, both Glx and Glu (-14.3%, p =.03) showed a significant decrease. There was no significant group effect for the neuronal marker NAA, creatine, choline or myo-inositol in either localization. CONCLUSIONS: This study suggests a possible role of altered glutamatergic neurotransmission within the anterior cingulate in the pathogenesis of mood disorders. The otherwise unremarkable findings of major brain metabolites confirms lack of neurodegenerative or membrane metabolic changes in major depression.

Altered white and gray matter metabolism in CADASIL: a proton MR spectroscopy and 1H-MRSI study.

OBJECTIVE: Subcortical white matter hyperintensities (WMH) and small cystic lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke in young adults. To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI). METHODS: Twenty patients with CADASIL and 21 age-matched controls were studied with 1H-MRSI at the level of the centrum semiovale; short echo time 1H-MRS was performed in six patients (WMH) and 10 controls. LCModel fits were used to estimate absolute and relative concentrations of N:-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr) within WMH, normal appearing white matter (NAWM), and cortical gray matter (GM) as well as myo-inositol (mI) and lactate in WMH. RESULTS: 1H-MRSI-Patients with CADASIL showed significantly reduced NAA, Cho, Cr, and total metabolite content (Met(tot)) in WMH and NAWM. Normalization to Met(tot) revealed that NAA/Met(tot) was reduced in all regions, whereas Cho and Cr were relatively elevated in WMH. Short echo time 1H-MRS showed decreased NAA, Cr, Met(tot), and NAA/Met(tot) and elevated mI/Met(tot) and lactate in WMH. Metabolite changes were larger in severely affected subjects. Rankin scores correlated negatively with NAA/Met(tot) (all regions) and NAA/Cho (WMH), and positively with Cho/Met(tot) (WMH) and Cr/Met(tot) (NAWM). CONCLUSION: Marked metabolic abnormalities were observed in abnormal and normal appearing white matter in patients with CADASIL. The findings suggest axonal injury, enlarged extracellular spaces, myelin loss, and gliosis. The cortical abnormalities may reflect structural damage or functional neuronal impairment secondary to white matter pathology. NAA reductions were correlated with clinical disability emphasizing the clinicopathologic relevance of axonal injury in CADASIL.

Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma.

Recently a new classification of primary cutaneous B-cell lymphomas (PCBCLs) has been proposed by the European Organization for Research and Treatment of Cancer (EORTC)--Cutaneous Lymphoma Project Group. The marginal zone B-cell lymphomas (MZLs) were not included as a distinct entity because of insufficient experience and controversial opinions. We have studied 32 patients (M:F ratio 1.5:1; age range 25-93 years; mean age 49.6 years; median age 50 years) to determine the diagnostic criteria of primary cutaneous MZL and the relationship with other low-grade malignant PCBCLs. For comparison, three patients with immunocytoma were included in the study. Clinically, patients presented with solitary or clustered reddish or red-brown papules, nodules, and plaques, sometimes surrounded by an erythematous halo. Histopathologic sections showed nodular or diffuse infiltrates involving the dermis and subcutaneous fat. Cytomorphologically small to medium-sized cells with indented nuclei and abundant pale cytoplasm (marginal zone cells, centrocyte-like cells) predominated. In addition, scattered blasts, lymphoplasmacytoid cells, and plasma cells were observed below the epidermis and at the periphery of the infiltrates. Reactive germinal centers were present in 75% of the cases. The three cases of immunocytoma showed a more monomorphous pattern with predominance of lymphoplasmacytoid cells. The marginal zone cells showed a CD20+, CD79a+, CD5- and Bcl-2+ immunophenotype. They expressed immunoglobulin G in the majority of the cases. Staining with the monocytoid B cell-related antibody KiM1p gave positive results in all specimens with a typical intracytoplasmic granular pattern. A monoclonal distribution of immunoglobulin light chains was observed in marginal zone cells in 75% of the cases. Germinal centers, when present, were either polyclonal or negative for both kappa and lambda light chains. Monoclonal rearrangement of the JH gene was detected via polymerase chain reaction (PCR) in 18 of 26 investigated specimens. Analysis in 12 patients of the bcl-2/immunoglobulin heavy chain gene rearrangement using PCR yielded negative results. Lesions were treated by surgical excision followed in some patients by local radiotherapy. Systemic antibiotic therapy was administered to three patients, with good response in two. The prognosis is excellent. After a mean follow-up of 47.9 months (range 6-252; median 24) all patients are alive without signs of systemic lymphoma. Primary cutaneous MZL represents a distinct clinicopathologic subtype of low-grade malignant PCBCL.

Anencephaly in one monoamniotic-monochorionic twin and encephalocele in the other.

This is a report of monoamniotic-monochorionic (ie, probably MZ) twins, one of which had anencephaly, whereas the co-twin died of complications of prematurity. Autopsy in this seemingly nonmalformed twin showed a small encephalocele. The literature on MZ twins with discordant anencephaly is often contradictory. It is suggested that this might be due to the difficulty of determining zygosity on the one hand and identifying discordance or concordance on the other. This case is presented as an example of this difficulty; it is discordant with respect to anencephaly, but concordant in the sense of "dysraphic" disturbances.

Influence of Epstein-Barr virus genomes on patient survival in Hodgkin's disease.

In previous studies, Epstein-Barr virus was considered a possible etiologic factor in Hodgkin's disease. Two hundred twenty-nine cases of Hodgkin's disease were investigated for the presence of Epstein-Barr virus DNA using the polymerase chain reaction technique on formalin-fixed, paraffin-embedded lymph node tissue to clarify the clinical importance of the incidence of this genome. In 42 cases (18.3%), genomic DNA was not amplifiable. The remaining 187 cases included the following subtypes: lymphocyte-predominant type (n = 13), nodular sclerosis type (n = 98), mixed cellularity type (n = 68), and lymphocyte-depleted type (n = 8). Sixty-six cases (35.2%) were positive for Epstein-Barr virus DNA. In the statistical analysis of available follow-up data from 130 patients, no influence of a positive Epstein-Barr virus DNA finding on length of survival time was revealed. This was true within the cohort of all patients and within the histologically defined subtypes of Hodgkin's disease. In this investigation, detection of Epstein-Barr virus DNA by polymerase chain reaction showed no prognostic relevance for patients with Hodgkin's disease.

Separate cerebellar areas for motor control.

Cerebellar activation was measured using functional magnetic resonance imaging, while seven normal subjects tapped their fingers paced by tone sequences with or without tone omission. The cerebellar anterior lobe (Larsell's H IV-V) ipsilateral to the movement was activated to a similar degree irrespective of the presence or absence of the tone omission. In contrast, the lateral part of the bilateral posterior lobe (H VIIa) was significantly highly activated for the tone sequence with random omission, compared with either that without omission or that with regular omission. The result suggests that the H IV-V is involved in motor execution, while the lateral part of H VIIa is involved in on-line motor adjustment to unpredictable sensory stimuli.

Stromelysin-3 (ST-3) mRNA expression in colorectal carcinomas. Localization and clinicopathologic correlations.

Stromelysin-3 (ST-3) mRNA expression was studied in 28 colorectal carcinomas and compared with that of adjacent nontumorous tissue. By Northern blot analysis, levels of ST-3 mRNA were significantly increased in the carcinomas compared with ST-3 expression was seen with degree of invasion, nodal or distant metastases, or histologic grade. In situ hybridization of nontumorous tissue showed no significant ST-3 expression. In tumor tissue, ST-3 mRNA was localized adjacent to colon carcinoma cells in irregular foci within the stoma. No significant difference in ST-3 expression was found between the center and periphery of the colon tumors. Most of the colon carcinomas (26 of 28) induced an expression of ST-3 in the directly adjacent stroma. No significant correlation between ST-3 mRNA expression and tumor stage and grade was seen. By Northern blot, we also saw expression of ST-3 in noncarcinomatous tissue, further supporting the concept that ST-3 expression is a tumor-induced but not a tumor-specific phenomenon.

Abnormal neural fold development in mouse trisomy 12 and trisomy 14. II. LM and TEM.

LM and TEM observations of embryonic tissue during the period of cranial neurulation are described in trisomic mouse embryos known to develop exencephaly, and are compared with tissue from normal mouse embryos. The earliest regularly observed differences were visible from the late presomite stage onwards, in the extracellular matrix of the cranial region. These were local defects of the basement membrane of the neural epithelium and enlarged areas of mesenchymal extracellular matrix, with associated abnormalities of mesenchymal cell distribution, cell number and cell contacts, and deficiency of alcian blue staining. Apical neuroepithelial microfilament bundles were observed at later somite-stages in trisomic embryos c.f. = compared with controls, and development of the concave neuroepithelial curvature was correspondingly retarded. Apposition of the neural folds at the forebrain/midbrain junction was never made, even though late neural fold fusion occurred in the hindbrain and ventral forebrain. At later stages (9-20 somites) the neuroepithelial cells showed pyknotic nuclei and dense intracellular inclusions. These are interpreted as secondary effects.

In vitro evaluation of different remineralization periods in improving the resistance of previously eroded bovine dentine against tooth-brushing abrasion.

One dentine specimen was prepared from each of 90 bovine incisors. The samples were then evenly distributed among nine groups (A-I) and submitted to 10 alternating de- and re-mineralization cycles, including abrasion by tooth brushing. Each cycle started with a demineralization using the erosive soft drink Sprite Light for 1 min, followed by storing the samples in pooled human saliva for a total of 240 min. The specimens were removed from the saliva at different intervals (group A, 0 min; B, 15 min; C, 30 min; D, 45 min; E, 60 min; F, 90 min; G, 120 min) and brushed in an automatic brushing machine. Groups H (erosion, but no brushing) and I (no erosion, but brushing), which were also stored in saliva for 240 min, served as controls. After these cycles, loss of dentine was determined by profilometry, producing the following values (mean+/-S.D.), which were analysed statistically (P< or = 0.05): group A (5.03+/-1.49 microm), B (4.44+/-1.09 microm), C (4.91+/-0.95 microm), D (5.47+/-1.52 microm), E (5.29+/-1.45 microm), F (4.76+/-0.74 microm), G (5.16+/-0.71 microm), H (2.61+/-1.31), I (1.11+/-0.39). Groups A-G had no significant differences, but they showed a significantly greater loss of dentine than groups H and I. It is concluded that the abrasion resistance of eroded bovine dentine is still decreased after a remineralization period of 120 min.

Cost-effective GPU-grid for genome-wide epistasis calculations.

BACKGROUND: Until recently, genotype studies were limited to the investigation of single SNP effects due to the computational burden incurred when studying pairwise interactions of SNPs. However, some genetic effects as simple as coloring (in plants and animals) cannot be ascribed to a single locus but only understood when epistasis is taken into account [1]. It is expected that such effects are also found in complex diseases where many genes contribute to the clinical outcome of affected individuals. Only recently have such problems become feasible computationally. OBJECTIVES: The inherently parallel structure of the problem makes it a perfect candidate for massive parallelization on either grid or cloud architectures. Since we are also dealing with confidential patient data, we were not able to consider a cloud-based solution but had to find a way to process the data in-house and aimed to build a local GPU-based grid structure. METHODS: Sequential epistatsis calculations were ported to GPU using CUDA at various levels. Parallelization on the CPU was compared to corresponding GPU counterparts with regards to performance and cost. RESULTS: A cost-effective solution was created by combining custom-built nodes equipped with relatively inexpensive consumer-level graphics cards with highly parallel GPUs in a local grid. The GPU method outperforms current cluster-based systems on a price/performance criterion, as a single GPU shows speed performance comparable up to 200 CPU cores. CONCLUSION: The outlined approach will work for problems that easily lend themselves to massive parallelization. Code for various tasks has been made available and ongoing development of tools will further ease the transition from sequential to parallel algorithms.