Reliability map of individual differences reflected in inter-subject correlation in naturalistic imaging.

Understanding individual differences in brain function is an essential aim of neuroscience. Naturalistic imaging links neural activity to real-life contexts and reflects individual differences in brain response. These unique features make it a promising tool for individualized psychiatry. An essential prerequisite for the extensive use of this paradigm is the reliable representation of inter-individual relationships. We used a test-retest approach to examine whether the naturalistic paradigm reliably represents inter-individual differences, which brain regions have the superior capability, and whether the ability alters with the contents of the stimuli. We quantified the reliability of the inter-subject relationships in repeated scans of two movie clips: a natural sight view and an emotion-evoking story. Besides statistical inference, we included resting-state scans, behavioral tests, and questionnaires as references for the comparison. The results showed that over one-third area of the brain could reliably characterize the inter-individual relationship, and the superior temporal lobe demonstrated comparable reliability representation with the State and Trait Anxiety Inventory. Furthermore, the temporal lobe regions could retain this capability across emotional movies with different contents. This study provides a base for pushing the naturalistic imaging paradigm towards clinical applications and proposes reliable target brain regions for future studies.

Uncovering cortical activations of discourse comprehension and their overlaps with common large-scale neural networks.

We conducted a meta-analysis of 78 task-based functional magnetic resonance imaging (fMRI) studies (1976 total participants) to reveal underlying brain activations and their overlap with large-scale neural networks in the brain during general discourse comprehension and its sub-processes. We found that discourse comprehension involved a neural system consisting of widely distributed brain regions that comprised not only the bilateral perisylvian language zones, but also regions in the superior and medial frontal cortex and the medial temporal lobe. Moreover, this neural system can be categorized into several sub-systems representing various sub-processes of discourse comprehension, with the left inferior frontal gyrus and middle temporal gyrus serving as core regions across all sub-processes. At a large-scale network level, we found that discourse comprehension relied most heavily on the default network, particularly on its dorsal medial subsystem. The pattern associated with large-scale network cooperation varied according to the respective sub-processes required. Our results reveal the functional dissociation within the discourse comprehension neural system and highlight the flexible involvements of large-scale networks.

Initiating PeriCBD to probe perinatal influences on neurodevelopment during 3-10 years in China.

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.

Optimizing network neuroscience computation of individual differences in human spontaneous brain activity for test-retest reliability.

A rapidly emerging application of network neuroscience in neuroimaging studies has provided useful tools to understand individual differences in intrinsic brain function by mapping spontaneous brain activity, namely intrinsic functional network neuroscience (ifNN). However, the variability of methodologies applied across the ifNN studies-with respect to node definition, edge construction, and graph measurements-makes it difficult to directly compare findings and also challenging for end users to select the optimal strategies for mapping individual differences in brain networks. Here, we aim to provide a benchmark for best ifNN practices by systematically comparing the measurement reliability of individual differences under different ifNN analytical strategies using the test-retest design of the Human Connectome Project. The results uncovered four essential principles to guide ifNN studies: (1) use a whole brain parcellation to define network nodes, including subcortical and cerebellar regions; (2) construct functional networks using spontaneous brain activity in multiple slow bands; and (3) optimize topological economy of networks at individual level; and (4) characterize information flow with specific metrics of integration and segregation. We built an interactive online resource of reliability assessments for future ifNN (https://ibraindata.com/research/ifNN).

Brief mock-scan training reduces head motion during real scanning for children: A growth curve study.

Pediatric neuroimaging datasets are rapidly increasing in scales. Despite strict protocols in data collection and preprocessing focused on improving data quality, the presence of head motion still impedes our understanding of neurodevelopmental mechanisms. Large head motion can lead to severe noise and artifacts in magnetic resonance imaging (MRI) studies, inflating correlations between adjacent brain areas and decreasing correlations between spatial distant territories, especially in children and adolescents. Here, by leveraging mock-scans of 123 Chinese children and adolescents, we demonstrated the presence of increased head motion in younger participants. Critically, a 5.5-minute training session in an MRI mock scanner was found to effectively suppress the head motion in the children and adolescents. Therefore, we suggest that mock scanner training should be part of the quality assurance routine prior to formal MRI data collection, particularly in large-scale population-level neuroimaging initiatives for pediatrics.

A longitudinal resource for population neuroscience of school-age children and adolescents in China.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

The impact of CoronaVac on the neutralization breadth and magnitude of the antibody response to SARS-CoV-2 viruses.

Although immune response enhancement has been reported after primary and booster vaccines of CoronaVac, neutralization breadth of SARS-CoV-2 variants is still unclear. In the present study, we examined the neutralization magnitude and breadth of SARS-CoV-2 variants including Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) in 33 convalescent COVID-19 patients and a cohort of 55 medical staff receiving primary CoronaVac vaccines and an additional homologous booster dose. Results showed that, as compared with the two-dose primary vaccination, the homologous booster dose achieved 2.24-, 3.98-, 4.58- and 2.90-fold increase in neutralization titer against wild-type, Beta, Delta, and Omicron, respectively. After booster dose, neutralization titer reduction for variants was less than that after the primary vaccine or that for convalescents. The proportion of recipients able to neutralize 2 or more variants increased from 36.36% post the primary vaccination to 87.27% after the booster. Significant increase in neutralization breadth of 1.24 (95% confidence interval (CI), 0.89-1.59) variants was associated with a log10 increase in neutralization titer against the wild-type. In addition, anti-RBD IgG level was identified as an excellent surrogate for positive neutralization of SARS-CoV-2 and neutralization breadth of variants. These findings highlight the value of an additional homologous CoronaVac dose in broadening the cross-neutralization against SARS-CoV-2 variants, and are critical for informing the booster dose vaccination efforts.

A Chinese multi-modal neuroimaging data release for increasing diversity of human brain mapping.

The big-data use is becoming a standard practice in the neuroimaging field through data-sharing initiatives. It is important for the community to realize that such open science effort must protect personal, especially facial information when raw neuroimaging data are shared. An ideal tool for the face anonymization should not disturb subsequent brain tissue extraction and further morphological measurements. Using the high-resolution head images from magnetic resonance imaging (MRI) of 215 healthy Chinese, we discovered and validated a template effect on the face anonymization. Improved facial anonymization was achieved when the Chinese head templates but not the Western templates were applied to obscure the faces of Chinese brain images. This finding has critical implications for international brain imaging data-sharing. To facilitate the further investigation of potential culture-related impacts on and increase diversity of data-sharing for the human brain mapping, we released the 215 Chinese multi-modal MRI data into a database for imaging Chinese young brains, namely'I See your Brains (ISYB)', to the public via the Science Data Bank ( https://doi.org/10.11922/sciencedb.00740 ).

Chinese Color Nest Project : An accelerated longitudinal brain-mind cohort.

The ongoing Chinese Color Nest Project (CCNP) was established to create normative charts for brain structure and function across the human lifespan, and link age-related changes in brain imaging measures to psychological assessments of behavior, cognition, and emotion using an accelerated longitudinal design. In the initial stage, CCNP aims to recruit 1520 healthy individuals (6-90 years), which comprises three phases: developing (devCCNP: 6-18 years, N = 480), maturing (matCCNP: 20-60 years, N = 560) and aging (ageCCNP: 60-84 years, N = 480). In this paper, we present an overview of the devCCNP, including study design, participants, data collection and preliminary findings. The devCCNP has acquired data with three repeated measurements from 2013 to 2017 in Southwest University, Chongqing, China (CCNP-SWU, N = 201). It has been accumulating baseline data since July 2018 and the second wave data since September 2020 in Chinese Academy of Sciences, Beijing, China (CCNP-CAS, N = 168). Each participant in devCCNP was followed up for 2.5 years at 1.25-year intervals. The devCCNP obtained longitudinal neuroimaging, biophysical, social, behavioral and cognitive data via MRI, parent- and self-reported questionnaires, behavioral assessments, and computer tasks. Additionally, data were collected on children's learning, daily life and emotional states during the COVID-19 pandemic in 2020. We address data harmonization across the two sites and demonstrated its promise of characterizing the growth curves for the overall brain morphometry using multi-center longitudinal data. CCNP data will be shared via the National Science Data Bank and requests for further information on collaboration and data sharing are encouraged.

Antipsychotic Effects on Cortical Morphology in Schizophrenia and Bipolar Disorders.

Background: Previous studies of atypical antipsychotic effects on cortical structures in schizophrenia (SZ) and bipolar disorder (BD) have findings that vary between the short and long term. In particular, there has not been a study exploring the effects of atypical antipsychotics on age-related cortical structural changes in SZ and BD. This study aimed to determine whether mid- to long-term atypical antipsychotic treatment (mean duration = 20 months) is associated with cortical structural changes and whether age-related cortical structural changes are affected by atypical antipsychotics. Methods: Structural magnetic resonance imaging images were obtained from 445 participants consisting of 88 medicated patients (67 with SZ, 21 with BD), 84 unmedicated patients (50 with SZ, 34 with BD), and 273 healthy controls (HC). Surface-based analyses were employed to detect differences in thickness and area among the three groups. We examined the age-related effects of atypical antipsychotics after excluding the potential effects of illness duration. Results: Significant differences in cortical thickness were observed in the frontal, temporal, parietal, and insular areas and the isthmus of the cingulate gyrus. The medicated group showed greater cortical thinning in these regions than the unmediated group and HC; furthermore, there were age-related differences in the effects of atypical antipsychotics, and these effects did not relate to illness duration. Moreover, cortical thinning was significantly correlated with lower symptom scores and Wisconsin Card Sorting Test (WCST) deficits in patients. After false discovery rate correction, cortical thinning in the right middle temporal gyrus in patients was significantly positively correlated with lower HAMD scores. The unmedicated group showed only greater frontotemporal thickness than the HC group. Conclusion: Mid- to long-term atypical antipsychotic use may adversely affect cortical thickness over the course of treatment and ageing and may also result in worsening cognitive function.

Efficacy and safety of berberine in the treatment of type 2 diabetes with insulin resistance: Protocol for a systematic review.

BACKGROUND: The incidence of diabetes mellitus (DM) is increasing year by year, and various complications can endanger the lives of patients. Type 2 diabetes mellitus (T2DM) accounts for more than 90% of DM, most of which is associated with insulin resistance (IR), and IR has been shown to be closely related to the onset of T2DM and the presence of DM complications. Berberine (BBR) has been shown to improve T2DM with IR in a number of ways. In this study, we aim to evaluate the efficacy and safety of BBR in the treatment of T2DM with IR to provide the newest evidence for clinical use. METHODS AND ANALYSIS: Literature research will be divided into 2 parts: electronic search and manual search. We will search PubMed, EMBASE, The Cochrane Library, the China National Knowledge Infrastructure, China Biology Medicine disc, the China Science and Technology Journal database, and the Wanfang database online. We will select the eligible studies published up to June 30, 2019. Dissertations, conference papers, ongoing trials, internal reports, etc., are searched by manual search methods. We use Homeostatic Model Assessment for IR (HOMA-IR) as the primary outcome of T2DM with IR, and we will also focus on the patient's blood glucose levels and all adverse reactions that occur during medication.Two reviewers will read the articles, extract the data information, and assess the risk of bias independently. Data analysis will use the software such as RevMan 5.3.5, ENDNOTE X7, and STATA 13.0. RESULTS: This study will provide a high-quality synthesis of current evidence of BBR for T2DM with IR from several aspects including HOMA-IR, blood glucose levels, and adverse events. CONCLUSION: This systematic review will provide evidence to assess the efficacy and safety of BBR in the treatment of T2DM with IR. ETHICS AND DISSEMINATION: Because all of the data used in this systematic review has been published, ethical approval is not required. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019123225.

Segregated precuneus network and default mode network in naturalistic imaging.

A resting-state network centered at the precuneus has been recently proposed as a precuneus network (PCUN) or "parietal memory network". Due to its spatial adjacency and overlapping with the default mode network (DMN), it is still not consensus to consider PCUN and DMN separately. Whether considering PCUN and DMN as different networks is a critical question that influences our understanding of brain functions and impairments. Previous resting-state studies using multiple methodologies have demonstrated a robust separation of the two networks. However, since there is no gold standard in justifying the functional difference between the networks in resting-state, we still lack of biological evidence to directly support the separation of the two networks. This study compared the responses and functional couplings of PCUN and DMN when participants were watching a movie and examined how the continuity of the movie context modulated the response of the networks. We identified PCUN and DMN in resting-state fMRI of 48 healthy subjects. The networks' response to a context-rich video and its context-shuffled version was characterized using the variance of temporal fluctuations and functional connectivity metrics. The results showed that (1) scrambling the contextual information altered the fluctuation level of DMN and PCUN in reversed ways; (2) compared to DMN, the FC within PCUN showed significantly higher sensitivity to the contextual continuity; (3) PCUN exhibited a significantly stronger functional network connectivity with the primary visual regions than DMN. These findings provide evidence for the distinct functional roles of PCUN and DMN in processing context-rich information and call for separately considering the functions and impairments of these networks in resting-state studies.

Anxiety correlates with cortical surface area in subjective cognitive decline: APOE ε4 carriers versus APOE ε4 non-carriers.

BACKGROUND: Subjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ε4 allele is thought to be a genetic marker associated with risk of SCD. Neuropsychiatric symptoms may provide insight in detecting higher-risk elders for early Alzheimer's disease as well. Therefore, we aim to explore the characteristics of brain morphology in SCD and to determine whether it is influenced by APOE ε4 as well as neuropsychiatric symptoms in SCD. METHODS: A total of 138 cognitively normal older individuals from the SILCODE cohort underwent a clinical interview, neuropsychological assessments, a blood test, and MRI. A two-sample t-test was used to examine the cortex volume and bilateral cortical surface area alterations between SCD (n = 65) and controls (n = 73). A general linear model analysis was used to test for both main and interaction effects of clinical phenotype (SCD vs. controls) and APOE on global and regional cortex volume and bilateral cortical surface area and thickness. A multiple linear regression analysis was conducted to determine the effects of the APOE genotype on the relationships between morphometric features and neuropsychiatric symptoms in SCD. RESULTS: Compared with controls, individuals with SCD showed decreased total cortical volumes and cortical surface area. SCD APOE ε4 carriers showed additive reduction in the right cortical surface area. The evaluation scores of anxiety symptoms were negatively associated with the right cortical surface area in SCD APOE 4 non-carriers. CONCLUSIONS: Individuals with SCD had an altered cortical surface area, and APOE genotype and anxiety symptoms are modified factors on the cortical surface area decrease in SCD. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT03370744 ). Registered 15 March 2017.

Functional Connectivity Changes Across the Spectrum of Subjective Cognitive Decline, Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

The abnormality occurs at molecular, cellular as well as network levels in patients with Alzheimer's disease (AD) prior to diagnosis. Most previous connectivity studies were conducted at 1 out of 3 (local, meso and global) scales in subjects covering only part of the entire AD spectrum (subjective cognitive decline, SCD; amnestic mild cognitive impairment, aMCI; and then fully manifest AD). Data interpretation within the framework of disease progression is therefore difficult. The current study included 3 age- and sex-matched cohorts: SCD (n = 32), aMCI (n = 37) and fully-established AD (n = 30). A group of healthy elderly subjects (n = 40) were included as a normal control (NC). Network connectivity was examined at the local (degree centrality), meso [subgraph centrality (SC)], and global (eigenvector and page-rank centralities) levels. As compared to NC, SCD subjects had isolated decrease of SC in primary (somatomotor and visual) networks. aMCI subjects had decreased centralities at all three scales in associative (frontoparietal control, dorsal attention, limbic and default) networks. AD subjects had increased centrality at the global scale in all seven networks. There was a positive association between Montreal Cognitive Assessment (MoCA) scores and DC in the frontoparietal control network in SCD, a negative relationship between Mini-Mental State Examination (MMSE) scores and EC in the somatomotor network in AD. These findings suggest that the primary network is impaired as early as in SCD. Impairment in the associative network also starts at the local level at this stage and may contribute to the cognitive decline. As associative network impairment extends from local to meso and global scales in aMCI, compensatory mechanisms in the primary network are activated.

Reduced bioavailability and plant uptake of polycyclic aromatic hydrocarbons from soil slurry amended with biochars pyrolyzed under various temperatures.

Biochar has high potential for organic pollutant immobilization due to its powerful sorption capacity. Nevertheless, potential risks may exist when biochar-sorbed organic pollutants are bioavailable. A direct plant exposure assay in combination with an organic solvent extraction experiment was carried out in this study to investigate the bioavailability of polycyclic aromatic hydrocarbons (PAHs) with the application of pine needle biochars pyrolyzed under different temperatures (100, 300, 400, and 700 °C; referred as P100-P700 accordingly). Biochar reduced solvent extractability and plant uptake of PAHs including naphthalene (Naph), acenaphthene (Acen), phenanthrene (Phen), and pyrene (Pyr), especially for three- and four-ring PAHs (Phen and Pyr) with high-temperature biochar. Plant uptake assay validates with organic solvent extraction for bioavailability assessment. Sorption of PAHs to biochars reduced plant uptake of PAHs in roots and shoots by lowering freely dissolved PAHs. Aging process reduced the bioavailability of PAHs that were bound to biochar. High pyrolysis temperature can be recommended for biochar preparation for purpose of effectively immobilizing PAHs, whereas application of moderate-temperature biochar for PAH immobilization should concern the potential risks of desorption and bioavailability of PAHs.

Homotopic Connectivity in Early Pontine Infarction Predicts Late Motor Recovery.

Connectivity-based methods are essential to explore brain reorganization after a stroke and to provide meaningful predictors for late motor recovery. We aim to investigate the homotopic connectivity alterations during a 180-day follow-up of patients with pontine infarction to find an early biomarker for late motor recovery prediction. In our study, resting-state functional MRI was performed in 15 patients (11 males, 4 females, age: 57.87 ± 6.50) with unilateral pontine infarction and impaired motor function during a period of 6 months (7, 14, 30, 90, and 180 days after stroke onset). Clinical neurological assessments were performed using the Fugl-Meyer scale (FM).15 matched healthy volunteers were also recruited. Whole-brain functional homotopy in each individual scan was measured by voxel-mirrored homotopic connectivity (VMHC) values. Group-level analysis was performed between stroke patients and normal controls. A Pearson correlation was performed to evaluate correlations between early VMHC and the subsequent 4 visits for behavioral measures during day 14 to day 180. We found in early stroke (within 7 days after onset), decreased VMHC was detected in the bilateral precentral and postcentral gyrus and precuneus/posterior cingulate cortex (PCC), while increased VMHC was found in the hippocampus/amygdala and frontal pole (P < 0.01). During follow-up, VMHC in the precentral and postcentral gyrus increased to the normal level from day 90, while VMHC in the precuneus/PCC presented decreased intensity during all time points (P < 0.05). The hippocampus/amygdala and frontal pole presented a higher level of VMHC during all time points (P < 0.05). Negative correlation was found between early VMHC in the hippocampus/amygdala with FM on day 14 (r = -0.59, p = 0.021), day 30 (r = -0.643, p = 0.01), day 90 (r = -0.693, p = 0.004), and day 180 (r = -0.668, p = 0.007). Furthermore, early VMHC in the frontal pole was negatively correlated with FM scores on day 30 (r = -0.662, p = 0.013), day 90 (r = -0.606, p = 0.017), and day 180 (r = -0.552, p = 0.033). Our study demonstrated the potential utility of early homotopic connectivity for prediction of late motor recovery in pontine infarction.

Local-to-remote cortical connectivity in amnestic mild cognitive impairment.

Alterations in both local and remote connectivity were reported in amnestic mild cognitive impairment (aMCI) patients but rarely in the same group of patients. In the present study, we employed a novel resting-state functional magnetic resonance imaging (rfMRI) connectome index, regional functional homogeneity on the 2-dimensional cortical surface, to detect full-cortex vertex-wise changes of the local rfMRI connectivity in 32 aMCI patients compared with 40 healthy controls. We further used the seed-based functional connectivity to explore the remote rfMRI connectivity in aMCI. The results revealed significantly lower local connectivity in the default network and higher local connectivity in the somatomotor network in aMCI patients. Abnormal remote connectivity relevant to local connectivity was primarily detectable within the default network (decrease) and in the somatomotor and attention networks (increase). The abnormalities in the remote (not local) default network connectivity were significantly associated with episodic memory performance in patients. These distance-related connectivity profiles illustrated a dysfunctional pattern in aMCI, which extended our knowledge of this pathological aging process.

Segregation between the parietal memory network and the default mode network: effects of spatial smoothing and model order in ICA.

A brain network consisting of two key parietal nodes, the precuneus and the posterior cingulate cortex, has emerged from recent fMRI studies. Though it is anatomically adjacent to and spatially overlaps with the default mode network (DMN), its function has been associated with memory processing, and it has been referred to as the parietal memory network (PMN). Independent component analysis (ICA) is the most common data-driven method used to extract PMN and DMN simultaneously. However, the effects of data preprocessing and parameter determination in ICA on PMN-DMN segregation are completely unknown. Here, we employ three typical algorithms of group ICA to assess how spatial smoothing and model order influence the degree of PMN-DMN segregation. Our findings indicate that PMN and DMN can only be stably separated using a combination of low-level spatial smoothing and high model order across the three ICA algorithms. We thus argue for more considerations on parametric settings for interpreting DMN data.

[Study on Pseudomonas sp. WBC-3 capable of complete degradation of methylparathion].

A bacterial strain was isolated from the polluted soil around Shashi Pesticides Factory, which was capable of complete degradation of methylparathion. Through chemotaxonomic characterizations and phylogenetic inference based on 16S rDNA sequence analysis, the strain was identified as a member of the genus and was named as Pseudomonas sp. WBC-3. It can tolerate high-concentration methylparathion up to 800 mg/L in basic medium and up to 2000 mg/L in 0.1% glucose medium. Using 300 mg/L methylparathion as its sole carbon and nitrogen sources, the strain was able to degrade 15 mg of parathion per liter per hour and reached its stationary phase in about 22 hours. The strain possessed broad-spectrum degradative capability to kinds of organophosphorus pesticides and aromatic compounds. Its organophosphate hydrolase was purified from the periplasm of WBC-3 to homogeneity, through a whose process consisting of ammonium sulfate precipitation, Sephadex G-75 gel filtration, Q Sepharose FF ionexchange column chromatography. The purified enzyme showed a single band on SDS-PAGE gel with an approximate molecular weight of 33.5 kD.