Purification and characterisation of endo-β-1,4-glucanase and laminarinase enzymes from the gecarcinid land crab Gecarcoidea natalis and the aquatic crayfish Cherax destructor

Laminarinase and endo-&beta;-1,4-glucanase were purified and characterised from the midgut gland of the herbivorous land crab Gecarcoidea natalis and the crayfish Cherax destructor. The laminarinase isolated from G. natalis was estimated to have a molecular mass of 41 kDa by SDS-PAGE and 71 kDa by gel filtration chromatography. A similar discrepancy was noted for C. destructor. Possible reasons for this are discussed. Laminarinase (EC 3.2.1.6) from G. natalis had a Vmax of 42.0 &micro;mol reducing sugars produced min&ndash;1 mg protein&ndash;1, a Km of 0.126% (w/v) and an optimum pH range of 5.5&ndash;7, and hydrolysed mainly &beta;-1,3-glycosidic bonds. In addition to the hydrolysis of &beta;-1,3-glycosidic bonds, laminarinase (EC 3.2.1.39) from C. destructor was capable of significant hydrolysis of &beta;-1,4-glycosidic bonds. It had a Vmax of 19.6 &micro;mol reducing sugars produced min&ndash;1 mg protein&ndash;1, a Km of 0.059% (w/v) and an optimum pH of 5.5. Laminarinase from both species produced glucose and other short oligomers from the hydrolysis of laminarin. Endo-&beta;-1,4-glucanase (EC 3.2.1.4) from G. natalis had a molecular mass of 52 kDa and an optimum pH of 4&ndash;7. It mainly hydrolysed &beta;-1,4-glycosidic bonds, but was also capable of significant hydrolysis of &beta;-1,3-glycosidic bonds. Two endo-&beta;-1,4-glucanases, termed 1 and 2, with respective molecular masses of 53&plusmn;3 and 52 kDa, were purified from C. destructor. Endo-&beta;-1,4-glucanase 1 was only capable of hydrolysing &beta;-1,4-glycosidic bonds and had an optimum pH of 5.5. Endo-&beta;-1,4-glucanases from both species produced some glucose, cellobiose and other short oligomers from the hydrolysis of carboxymethyl cellulose. <br /

Metal-based drugs that break the rules

Cisplatin and other platinum compounds have had a huge impact in the treatment of cancers and are applied in the majority of anticancer chemotherapeutic regimens. The success of these compounds has biased the approaches used to discover new metal-based anticancer drugs. In this perspective we highlight compounds that are apparently incompatible with the more classical (platinum-derived) concepts employed in the development of metal-based anticancer drugs, with respect to both compound design and the approaches used to validate their utility. Possible design approaches for the future are also suggested

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This is the published version: Allardyce, Benjamin J., Linton, Stuart M. and Saborowski, Reinhard 2010, The last piece in the cellulase puzzle : the characterisation of β-glucosidase from the herbivorous gecarcinid land crab Gecarcoidea natalis, Journal of experimental biology, vol. 213, no. 17, pp. 2950-2957. Available from Deakin Research Online: http://hdl.handle.net/10536/DRO/DU:30031463 Reproduced with the kind permissions of the copyright owner. Copyright : 2010, Company of Biologists 2950 INTRODUCTION Herbivorous terrestrial crustaceans, such as gecarcinid land crabs, consume a wide range of plant material, which is rich in cellulose and hemicellulose. Land crabs possess multiple endogenous endo--1,4-glucanases, one of the key enzyme classes involved in cellulose hydrolysis The traditional model for cellulose digestion in invertebrates reflects what is known about fungal cellulase systems. This model suggests that cellulose hydrolysis involves the synergistic activity of endo--1,4-glucanases (1,4--D-glucan-4-glucanohydrolases, EC 3.2.1.4), exoglucanases, including both cellobiohydrolases (1,4--D-glucan cellobiohydrolases, EC 3.2.1.91) and sometimes glucohydrolases (1,4--D-glucan glucanohydrolases, EC 3.2.1.74) and -glucosidases (-glucoside glucohydrolases, EC 3.2.1.21) Like fungal systems, endo--1,4-glucanases and -glucosidases appear to be key components of the cellulase systems of many marine and terrestrial invertebrate

Early-life inflammatory markers and subsequent psychotic and depressive episodes between 10 to 28 years of age

Inflammation is implicated in depression and psychosis, including association of childhood inflammatory markers on the subsequent risk of developing symptoms. However, it is unknown whether early-life inflammatory markers are associated with the number of depressive and psychotic symptoms from childhood to adulthood. Using the prospective Avon Longitudinal Study of Children and Parents birth cohort (N = up-to 6401), we have examined longitudinal associations of early-life inflammation [exposures: interleukin-6 (IL-6), C-reactive protein (CRP) levels at age 9y; IL-6 and CRP DNA-methylation (DNAm) scores at birth and age 7y; and IL-6 and CRP polygenic risk scores (PRSs)] with the number of depressive episodes and psychotic experiences (PEs) between ages 10–28 years. Psychiatric outcomes were assessed using the Short Mood and Feelings Questionnaire and Psychotic Like Symptoms Questionnaires, respectively. Exposure-outcome associations were tested using negative binomial models, which were adjusted for metabolic and sociodemographic factors. Serum IL-6 levels at age 9y were associated with the total number of depressive episodes between 10 and 28y in the base model (n = 4835; β = 0.066; 95%CI:0.020–0.113; pFDR = 0.041) which was weaker when adjusting for metabolic and sociodemographic factors. Weak associations were observed between inflammatory markers (serum IL-6 and CRP DNAm scores) and total number of PEs. Other inflammatory markers were not associated with depression or PEs. Early-life inflammatory markers are associated with the burden of depressive episodes and of PEs subsequently from childhood to adulthood. These findings support a potential role of early-life inflammation in the aetiology of depression and psychosis and highlight inflammation as a potential target for treatment and prevention

An impinging remnant meniscus causing early polyethylene failure in total knee arthroplasty: a case report

The management of patients with an apparently normal functional total knee arthroplasty (TKA) suffering from unexplained persistent pain and swelling is a challenging issue. The usual causes of pain after total knee replacement are well known, but there are a small number of patients in whom its aetiology is obscure. Malfunction due to soft tissue impingement has rarely been reported. A patient with an unusual case of posterior soft tissue impingement secondary to a trapped posterior horn of a remnant medial meniscus after TKA and responsible for severe early polyethylene wear, is reported. The diagnosis was confirmed by arthroscopy. Treatment was performed by arthrotomy. The meniscus remnant was removed followed by total synovectomy and isolated exchange of the polyethylene insert. To our knowledge, this is the first well-documented case reporting this association

Working with Young People Who Offend : An Examination of the Literature Regarding Violence, Substance Misuse and Harmful Sexual Behaviour

This paper presents a review of the recent literature relating to effective practice with young people displaying harmful sexual behaviour (HSB), violence or risky substance misuse. The intention is to build upon and update the 2007 literature review Research and practice in risk assessment and risk management of children and young people engaging in offending behaviour, funded by the Risk Management Authority (RMA) and carried out by the Scottish Centre for Crime and Justice Research (SCCJR)

Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder

Importance Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms. Objectives To investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and level of mood-incongruent psychotic features. Design Case-control design: using multinomial logistic regression, to estimate differential associations of PRS across categories of cases and controls. Settings & Participants 4399 BD cases, 2966 (67%) female, mean age-at-interview 46 [sd 12] years, from the BD Research Network (BDRN) were included in the final analyses. For comparison genotypic data for 4976 schizophrenia cases and 9012 controls from the Type-1 diabetes genetics consortium and Generation Scotland were included. Exposure Standardised PRS, calculated using alleles with an association p-value threshold < 0.05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, adjusted for the first 10 population principal components and genotyping-platform. Main outcome measure Multinomial logit models estimated PRS associations with BD stratified by (1) Research Diagnostic Criteria (RDC) BD subtypes (2) Lifetime occurrence of psychosis.(3) Lifetime mood-incongruent psychotic features and (4) ordinal logistic regression examined PRS associations across levels of mood-incongruence. Ratings were derived from the Schedule for Clinical Assessment in Neuropsychiatry interview (SCAN) and the Bipolar Affective Disorder Dimension Scale (BADDS). Results Across clinical phenotypes, there was an exposure-response gradient with the strongest PRS association for schizophrenia (RR=1.94, (95% C.I. 1.86, 2.01)), then schizoaffective BD (RR=1.37, (95% C.I. 1.22, 1.54)), BD I (RR= 1.30, (95% C.I. 1.24, 1.36)) and BD II (RR=1.04, (95% C.I. 0.97, 1.11)). Within BD cases, there was an effect gradient, indexed by the nature of psychosis, with prominent mood-incongruent psychotic features having the strongest association (RR=1.46, (95% C.I. 1.36, 1.57)), followed by mood-congruent psychosis (RR= 1.24, (95% C.I. 1.17, 1.33)) and lastly, BD cases with no history of psychosis (RR=1.09, (95% C.I. 1.04, 1.15)). Conclusion We show for the first time a polygenic-risk gradient, across schizophrenia and bipolar disorder, indexed by the occurrence and level of mood-incongruent psychotic symptoms

Associations Between Schizophrenia Polygenic Liability, Symptom Dimensions, and Cognitive Ability in Schizophrenia

Importance Schizophrenia is a clinically heterogeneous disorder. It is currently unclear how variability in symptom dimensions and cognitive ability is associated with genetic liability for schizophrenia. Objective To determine whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence. Design, Setting, and Participants In a genetic association study, 3 cross-sectional samples of 1220 individuals with a diagnosis of schizophrenia were recruited from community, inpatient, and voluntary sector mental health services across the UK. Confirmatory factor analysis was used to create phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the MATRICS Consensus Cognitive Battery. Analyses of polygenic risk scores (PRSs) were used to assess whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were associated with these phenotypic dimensions. Data collection for the cross-sectional studies occurred between 1993 and 2016. Data analysis for this study occurred between January 2019 and March 2021. Main Outcomes and Measures Outcome measures included phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability. Exposure measures included PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence. Results Of the 1220 study participants, 817 were men (67.0%). Participants’ mean (SD) age at interview was 43.10 (12.74) years. Schizophrenia PRS was associated with increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10−4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10−4). Current cognitive ability was associated with genetic liability to schizophrenia (β = −0.11; 95% CI, −0.19 to −0.04; P = 1.63 × 10−3) and intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10−10). After controlling for estimated premorbid IQ, current cognitive performance was associated with schizophrenia PRS (β = −0.08; 95% CI, −0.14 to −0.02; P = 8.50 × 10−3) but not intelligence PRS. Conclusions and Relevance The findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions. Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia