Purification and properties of a lipase from Penicillium chrysogenum isolated from industrial wastes

A fungal lipase was isolated from the wastes of industrial cultures of Penicillium chrysogenum employed in antibiotics production. Lipase activity was only detected in solid aggregates present in the protein concentrates. To extract the lipase, Triton X‐100 was the most suitable surfactant. The lipase was further purified by hydrophobic interaction and anion exchange chromatography. A molecular mass of approx 40 kDa and a pI of approx 3.8 were estimated. Optimum pH and temperature were 7.9–8.1 and 45 °C respectively. Although its activity in the hydrolysis of lipids and esters is not very high, the lipase from P chrysogenum proved to be notably efficient in several synthetic reactions in non‐aqueous media. © 2000 Society of Chemical Industry     

THE NYQUIST ROBUST STABILITY MARGIN—A NEW METRIC FOR THE STABILITY OF UNCERTAIN SYSTEMS

The Nyquist robust stability margin k_N is proposed as a new tool for analysing the robustness of uncertain systems. The analysis is done using Nyquist arguments involving eigenvalues instead of singular values, and yields exact necessary and sufficient conditions for robust stability. The concept of a critical line on the Nyquist plane is defined and used to calculate a critical perturbation radius which in turn is used to produce k_N. The new approach gives alternatives to computing exact stability margins in some cases of highly directional uncertainty templates where other models are not applicable. © 1997 by John Wiley & Sons, Ltd.     

Surimi gels from striped mullet (Mugil cephalus) employing microbial transglutaminase

Striped mullet (Mugil cephalus) is an abundant marine coastal fish of tropical waters and has a low commercial value. This work deals with the assessment of striped mullet as a resource for surimi gels. To improve the gels obtained, the addition of microbial transglutaminase was evaluated. Optimal conditions for setting were determined using mathematical models. Concentration of microbial transglutaminase (MTGase), temperature and time were studied to improve the mechanical properties of surimi gels from striped mullet. Shear stress was strongly affected by the variables studied while shear strain was moderately affected. Maximum shear stress (156 kPa) was obtained by employing the following setting conditions: a concentration of MTGase of 9.3 g/kg of surimi, a temperature of 37°C and a time of 3.9 h. Under these conditions the shear strain was 1.34. Maximum shear strain (1.57) was obtained by employing the following conditions: a concentration of MTGase of 5 g/kg of surimi, a temperature of 34.5°C and a time of 1 h. Under these conditions the shear stress was 123 kPa.     

Electroconvulsive Therapy in Psychiatric Disorders: A Narrative Review Exploring Neuroendocrine–Immune Therapeutic Mechanisms and Clinical Implications

Electroconvulsive therapy (ECT) is based on conducting an electrical current through the brain to stimulate it and trigger generalized convulsion activity with therapeutic ends. Due to the efficient use of ECT during the last years, interest in the molecular bases involved in its mechanism of action has increased. Therefore, different hypotheses have emerged. In this context, the goal of this review is to describe the neurobiological, endocrine, and immune mechanisms involved in ECT and to detail its clinical efficacy in different psychiatric pathologies. This is a narrative review in which an extensive literature search was performed on the Scopus, Embase, PubMed, ISI Web of Science, and Google Scholar databases from inception to February 2022. The terms “electroconvulsive therapy”, “neurobiological effects of electroconvulsive therapy”, “molecular mechanisms in electroconvulsive therapy”, and “psychiatric disorders” were among the keywords used in the search. The mechanisms of action of ECT include neurobiological function modifications and endocrine and immune changes that take place after ECT. Among these, the decrease in neural network hyperconnectivity, neuroinflammation reduction, neurogenesis promotion, modulation of different monoaminergic systems, and hypothalamus–hypophysis–adrenal and hypothalamus–hypophysis–thyroid axes normalization have been described. The majority of these elements are physiopathological components and therapeutic targets in different mental illnesses. Likewise, the use of ECT has recently expanded, with evidence of its use for other pathologies, such as Parkinson’s disease psychosis, malignant neuroleptic syndrome, post-traumatic stress disorder, and obsessive–compulsive disorder. In conclusion, there is sufficient evidence to support the efficacy of ECT in the treatment of different psychiatric disorders, potentially through immune, endocrine, and neurobiological systems.     

Risk Factors from Pregnancy to Adulthood in Multiple Sclerosis Outcome

Multiple sclerosis (MS) is an autoimmune disease characterized by a robust inflammatory response against myelin sheath antigens, which causes astrocyte and microglial activation and demyelination of the central nervous system (CNS). Multiple genetic predispositions and environmental factors are known to influence the immune response in autoimmune diseases, such as MS, and in the experimental autoimmune encephalomyelitis (EAE) model. Although the predisposition to suffer from MS seems to be a multifactorial process, a highly sensitive period is pregnancy due to factors that alter the development and differentiation of the CNS and the immune system, which increases the offspring’s susceptibility to develop MS. In this regard, there is evidence that thyroid hormone deficiency during gestation, such as hypothyroidism or hypothyroxinemia, may increase susceptibility to autoimmune diseases such as MS. In this review, we discuss the relevance of the gestational period for the development of MS in adulthood.     

双引擎勇士

历史总是让我们在"喷火"、"野马"、"零"式战斗机和令人恐惧的德国Bf-109等著名飞机上见识到二战的空中神话,它们都是一些单引擎战斗机.事实上我们忘记了,很多同样或类似的任务是由双引擎战机执行的.和它们的单引擎兄弟一样,双引擎飞机也在历史上赢得了一席之地,铸就不少空中传奇. 我们将在本期的杂志中向那些似乎总是被遗忘的...     

AC-265347 Inhibits Neuroblastoma Tumor Growth by Induction of Differentiation without Causing Hypocalcemia

Neuroblastoma is the most common extracranial solid tumor of childhood, with heterogeneous clinical manifestations ranging from spontaneous regression to aggressive metastatic disease. The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) that senses plasmatic fluctuation in the extracellular concentration of calcium and plays a key role in maintaining calcium homeostasis. We have previously reported that this receptor exhibits tumor suppressor properties in neuroblastoma. The activation of CaSR with cinacalcet, a positive allosteric modulator of CaSR, reduces neuroblastoma tumor growth by promoting differentiation, endoplasmic reticulum (ER) stress and apoptosis. However, cinacalcet treatment results in unmanageable hypocalcemia in patients. Based on the bias signaling shown by calcimimetics, we aimed to identify a new drug that might exert tumor-growth inhibition similar to cinacalcet, without affecting plasma calcium levels. We identified a structurally different calcimimetic, AC-265347, as a promising therapeutic agent for neuroblastoma, since it reduced tumor growth by induction of differentiation, without affecting plasma calcium levels. Microarray analysis suggested biased allosteric modulation of the CaSR signaling by AC-265347 and cinacalcet towards distinct intracellular pathways. No upregulation of genes involved in calcium signaling and ER stress were observed in patient-derived xenografts (PDX) models exposed to AC-265347. Moreover, the most significant upregulated biological pathways promoted by AC-265347 were linked to RHO GTPases signaling. AC-265347 upregulated cancer testis antigens (CTAs), providing new opportunities for CTA-based immunotherapies. Taken together, this study highlights the importance of the biased allosteric modulation when targeting GPCRs in cancer. More importantly, the capacity of AC-265347 to promote differentiation of malignant neuroblastoma cells provides new opportunities, alone or in combination with other drugs, to treat high-risk neuroblastoma patients.