Highly efficient novel recombinant L-asparaginase with no glutaminase activity from a new halo-thermotolerant Bacillus strain

Introduction: The bacterial enzyme has gained more attention in therapeutic application because of the higher substrate specificity and longer half-life. L-asparaginase is an important enzyme with known antineoplastic effect against acute lymphoblastic leukemia (ALL). Methods: Novel L-asparaginase genes were identified from a locally isolated halo-thermotolerant Bacillus strain and the recombinant enzymes were overexpressed in modified E. coli strains, OrigamiTM B and BL21. In addition, the biochemical properties of the purified enzymes were characterized, and the enzyme activity was evaluated at different temperatures, pH, and substrate concentrations. Results: The concentration of pure soluble enzyme obtained from Origami strain was ~30 mg/L of bacterial culture, which indicates the significant improvement compared to L-asparaginase produced by E. coli BL21 strain. The catalytic activity assay on the identified L-asparaginases (ansA1 and ansA3 genes) from Bacillus sp. SL-1 demonstrated that only ansA1 gene codes an active and stable homologue (ASPase A1) with high substrate affinity toward L-asparagine. The Kcat and Km values for the purified ASPase A1 enzyme were 23.96s-1 and 10.66 µM, respectively. In addition, the recombinant ASPase A1 enzyme from Bacillus sp. SL-1 possessed higher specificity to L-asparagine than L-glutamine. The ASPase A1 enzyme was highly thermostable and resistant to the wide range of pH 4.5�10. Conclusion: The biochemical properties of the novel ASPase A1 derived from Bacillus sp. SL-l indicated a great potential for the identified enzyme in pharmaceutical and industrial applications. © 2019 The Author(s)

Lateralization of inferior petrosal sinus sampling in Cushing's disease correlates with cavernous sinus venous drainage patterns, but not tumor lateralization

Background: Inferior petrosal sinus sampling (IPSS) is known as the gold standard to distinguish whether excessive adrenocorticotropin hormone (ACTH) production origins from the pituitary gland or an ectopic source. However, due to a number of factors, the value of IPSS for adenoma lateralization may be limited. Aim of this study was to evaluate the influence of parasellar venous drainage (VD) patterns on IPSS findings in predicting lateralization of pituitary microadenomas. Methods: We retrospectively reviewed records of confirmed cases of Cushing's disease which were evaluated by IPSS prior to endoscopic tansnasal trans-sphenoidal surgery (ETSS) to assess the ability of IPSS to predict adenoma laterality. Results: Seventeen patients with pathologically confirmed Cushing's disease were retrospectively reviewed. The median age of the included patients was 37 years. Laterality of parasellar VD perfectly associated with lateralization as measured by IPSS. Symmetrical VD was associated with symmetrical ACTH gradient on IPSS. However, lateralization measured by IPSS did not show any significant correlation with lateralization detected during ETSS. Conclusion: Our study suggests that IPSS lateralization results strongly depend on parasellar VD pattern but show no significant correlation with the adenoma lateralization found during ETSS. Thus, IPSS does not appear to be an appropriate modality to predict adenoma lateralization. © 2020 Anatomy; Neurology; Medical imaging; Endocrinology; Endocrine system; Clinical research; Inferior petrosal sinus sampling; Cushing's disease; Parasellar venous drainage; Lateralization of microadenoma © 202

Occurrence of Fusarium spp. and Fumonisins in Stored Wheat Grains Marketed in Iran

Wheat grains are well known to be invaded by Fusarium spp. under field and storage conditions and contaminated with fumonisins. Therefore, determining Fusarium spp. and fumonisins in wheat grains is of prime importance to develop suitable management strategies and to minimize risk. Eighty-two stored wheat samples produced in Iran were collected from various supermarkets and tested for the presence of Fusarium spp. by agar plate assay and fumonisins by HPLC. A total of 386 Fusarium strains were isolated and identified through morphological characteristics. All these strains belonged to F. culmorum, F. graminearum, F. proliferatum and F. verticillioides. Of the Fusarium species, F. graminearum was the most prevalent species, followed by F. verticillioides, F. proliferatum and then F. culmorum. Natural occurrence of fumonisin B1 (FB1) could be detected in 56 (68.2%) samples ranging from 15–155 μg/kg, fumonisin B2 (FB2) in 35 (42.6%) samples ranging from 12–86 μg/kg and fumonisin B3 (FB3) in 26 (31.7%) samples ranging from 13–64 μg/kg. The highest FB1 levels were detected in samples from Eilam (up to 155 μg/kg) and FB2 and FB3 in samples from Gilan Gharb (up to 86 μg/kg and 64 μg/kg)

Bioinformatics research in the Asia Pacific: a 2007 update

We provide a 2007 update on the bioinformatics research in the Asia-Pacific from the Asia Pacific Bioinformatics Network (APBioNet), Asia's oldest bioinformatics organisation set up in 1998. From 2002, APBioNet has organized the first International Conference on Bioinformatics (InCoB) bringing together scientists working in the field of bioinformatics in the region. This year, the InCoB2007 Conference was organized as the 6th annual conference of the Asia-Pacific Bioinformatics Network, on Aug. 27–30, 2007 at Hong Kong, following a series of successful events in Bangkok (Thailand), Penang (Malaysia), Auckland (New Zealand), Busan (South Korea) and New Delhi (India). Besides a scientific meeting at Hong Kong, satellite events organized are a pre-conference training workshop at Hanoi, Vietnam and a post-conference workshop at Nansha, China. This Introduction provides a brief overview of the peer-reviewed manuscripts accepted for publication in this Supplement. We have organized the papers into thematic areas, highlighting the growing contribution of research excellence from this region, to global bioinformatics endeavours

Mudanças nos compostos bioativos e atividade antioxidante de pimentas da região amazônica.

A Embrapa Amazônia Oriental possui um Banco Ativo de Pimenteira com diferentes genótipos do gênero Capsicum, os quais ainda não foram analisados, quanto às suas características funcionais e capacidade antioxidante. Este estudo objetivou determinar os teores de ácido ascórbico, compostos fenólicos, carotenoides totais e a atividade antioxidante total, em frutos imaturos e maduros de genótipos de pimentas Capsicum spp. As concentrações de vitamina C (100,76-361,65 mg 100 g-1 nos frutos imaturos e 36,70-157,76 mg 100 g-1 nos maduros) decresceram com a maturação dos frutos. Carotenoides totais não foram detectados nos frutos imaturos, porém, nos frutos maduros, observaram-se valores de 73,80-1349,97 mg g-1, em função do genótipo. Os teores de compostos fenólicos aumentaram nos frutos maduros (147,40-718,64 mg GAE 100 g-1), para oito dos nove genótipos avaliados. Os frutos de pimenteira apresentaram significativa atividade antioxidante (55,02-92,03 mM trolox g-1 nos frutos imaturos e 39,60-113,08 mM trolox g- 1 nos maduros). Concluiu-se que o grau de maturação dos frutos influenciou nos teores de compostos bioativos dos genótipos estudados. Destacaram-se, como genótipos promissores com potencial para serem utilizados em programas de melhoramento genético, IAN-186301 e IAN-186324, pelos altos teores de carotenoides totais; IAN-186301, IAN-186311, IAN-186312 e IAN-186313, com relação às altas concentrações de ácido ascórbico; IAN-186304 e IAN-186311, pelos altos teores de compostos fenólicos; e IAN-186311, para atividade antioxidante

Evaluation of the genotoxic and antigenotoxic potential of Melissa officinalis in mice

Melissa officinalis (L.) (Lamiaceae), a plant known as the lemon balm, is native to the east Mediterranean region and west Asia. Also found in tropical countries, such as Brazil, where it is popularly known as “erva-cidreira” or “melissa”, it is widely used in aqueous- or alcoholic-extract form in the treatment of various disorders. The aim was to investigate in vivo its antigenotoxicity and antimutagenicity, as well as its genotoxic/mutagenic potential through comet and micronucleus assaying. CF-1 male mice were treated with ethanolic (Mo-EE) (250 or 500 mg/kg) or aqueous (Mo-AE) (100 mg/kg) solutions of an M. officinalis extract for 2 weeks, prior to treatment with saline or Methyl methanesulfonate (MMS) doses by intraperitoneal injection. Irrespective of the doses, no genotoxic or mutagenic effects were observed in blood and bone-marrow samples. Although Mo-EE exerted an antigenotoxic effect on the blood cells of mice treated with the alkylating agent (MMS) in all the doses, this was not so with Mo-AE. Micronucleus testing revealed the protector effect of Mo-EE, but only when administered at the highest dose. The implication that an ethanolic extract of M. officinalis has antigenotoxic/antimutagenic properties is an indication of its medicinal relevance

2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects

Objective. The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods. Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results. Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion. Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis

Advances in mass spectrometry-based post-column bioaffinity profiling of mixtures

In the screening of complex mixtures, for example combinatorial libraries, natural extracts, and metabolic incubations, different approaches are used for integrated bioaffinity screening. Four major strategies can be used for screening of bioactive mixtures for protein targets—pre-column and post-column off-line, at-line, and on-line strategies. The focus of this review is on recent developments in post-column on-line screening, and the role of mass spectrometry (MS) in these systems. On-line screening systems integrate separation sciences, mass spectrometry, and biochemical methodology, enabling screening for active compounds in complex mixtures. There are three main variants of on-line MS based bioassays: the mass spectrometer is used for ligand identification only; the mass spectrometer is used for both ligand identification and bioassay readout; or MS detection is conducted in parallel with at-line microfractionation with off-line bioaffinity analysis. On the basis of the different fields of application of on-line screening, the principles are explained and their usefulness in the different fields of drug research is critically evaluated. Furthermore, off-line screening is discussed briefly with the on-line and at-line approaches