Music therapy for depression

Abstract not available. Full text available at https://onlinelibrary.wiley.com/doi/full/10.1002/nur.2200

Baeyer-Villiger Monooxygenases:Tunable Oxidative Biocatalysts

Pollution, accidents, and misinformation have earned the pharmaceutical and chemical industry a poor public reputation, despite their undisputable importance to society. Biotechnological advances hold the promise to enable a future of drastically reduced environmental impact and rigorously more efficient production routes at the same time. This is exemplified in the Baeyer-Villiger reaction, which offers a simple synthetic route to oxidize ketones to esters, but application is hampered by the requirement of hazardous and dangerous reagents. As an attractive alternative, flavin-containing Baeyer-Villiger monooxygenases (BVMOs) have been investigated for their potential as biocatalysts for a long time, and many variants have been characterized. After a general look at the state of biotechnology, we here summarize the literature on biochemical characterizations, mechanistic and structural investigations, as well as enzyme engineering efforts in BVMOs. With a focus on recent developments, we critically outline the advances toward tuning these enzymes suitable for industrial applications

Convergent cascade catalyzed by monooxygenase - alcohol dehydrogenase fusion applied in organic media

With the aim of applying redox-neutral cascade reactions in organic media, fusions of a type II flavin-containing monooxy-genase (FMO-E) and horse liver alcohol dehydrogenase (HLADH) were designed. The enzyme orientation and expression vector were found to influence the overall fusion enzyme activity. The resulting bi-functional enzyme retained the catalytic properties of both individual enzymes. The lyophilized cell free extract containing the bifunctional enzyme was applied for the convergent cascade reaction consisting of cyclobutanone and 1,4-butanediol in different micro-aqueous media with only 5% (v/v) aqueous buffer without any addition of external cofactor. Methyl tert-butyl ether and cyclopentyl methyl ether were found to be the best organic media for the synthesis of γ-butyrolactone resulting in ~27% analytical yield

Approaching boiling point stability of an alcohol dehydrogenase through computationally-guided enzyme engineering

Enzyme instability is an important limitation for the investigation and application of enzymes. Therefore, methods to rapidly and effectively improve enzyme stability are highly appealing. In this study we applied a computational method (FRESCO) to guide the engineering of an alcohol dehydrogenase. Of the 177 selected mutations, 25 mutations brought about a significant increase in apparent melting temperature (ΔTm ≥ +3 °C). By combining mutations, a 10-fold mutant was generated with a Tm of 94 °C (+51 °C relative to wildtype), almost reaching water's boiling point, and the highest increase with FRESCO to date. The 10-fold mutant's structure was elucidated, which enabled the identification of an activity-impairing mutation. After reverting this mutation, the enzyme showed no loss in activity compared to wildtype, while displaying a Tm of 88 °C (+45 °C relative to wildtype). This work demonstrates the value of enzyme stabilization through computational library design

Coupled reactions by coupled enzymes:alcohol to lactone cascade with alcohol dehydrogenase-cyclohexanone monooxygenase fusions

The combination of redox enzymes for redox-neutral cascade reactions has received increasing appreciation. An example is the combination of an alcohol dehydrogenase (ADH) with a cyclohexanone monooxygenase (CHMO). The ADH can use NADP(+) to oxidize cyclohexanol to form cyclohexanone and NADPH. Both products are then used by CHMO to produce ε-caprolactone. In this study, these two redox-complementary enzymes were fused, to create a self-sufficient bifunctional enzyme that can convert alcohols to esters or lactones. Three different ADH genes were fused to a gene coding for a thermostable CHMO, in both orientations (ADH-CHMO and CHMO-ADH). All six fusion enzymes could be produced and purified. For two of the three ADHs, we found a clear difference between the two orientations: one that showed the expected ADH activity, and one that showed low to no activity. The ADH activity of each fusion enzyme correlated with its oligomerization state. All fusions retained CHMO activity, and stability was hardly affected. The TbADH-TmCHMO fusion was selected to perform a cascade reaction, producing ε-caprolactone from cyclohexanol. By circumventing substrate and product inhibition, a > 99% conversion of 200 mM cyclohexanol could be achieved in 24 h, with > 13,000 turnovers per fusion enzyme molecule

A closer look into NADPH oxidase inhibitors: validation and insight into their mechanism of action

NADPH-oxidases (NOXs) purposefully produce reactive-oxygen-species (ROS) and are found in most kingdoms of life. The seven human NOXs are each characterized by a specific expression profile and a fine regulation to spatio-temporally tune ROS concentration in cells and tissues. One of the best known roles for NOXs is in host protection against pathogens but ROS themselves are important second messengers involved in tissue regeneration and the modulation of pathways that induce and sustain cell proliferation. As such, NOXs are attractive pharmacological targets in immunomodulation, fibrosis and cancer. We have studied an extensive number of available NOX inhibitors, with the specific aim to identify bona fide ligands versus ROS-scavenging molecules. Accordingly, we have established a comprehensive platform of biochemical and biophysical assays. Most of the investigated small molecules revealed ROS-scavenging and/or assay-interfering properties to various degrees. A few compounds, however, were also demonstrated to directly engage one or more NOX enzymes. Diphenylene iodonium was found to react with the NOXs’ flavin and heme prosthetic groups to form stable adducts. We also discovered that two compounds, VAS2870 and VAS3947, inhibit NOXs through the covalent alkylation of a cysteine residue. Importantly, the amino acid involved in covalent binding was found to reside in the dehydrogenase domain, where the nicotinamide ring of NADPH is bound. This work can serve as a springboard to guide further development of bona fide ligands with either agonistic or antagonistic properties toward NOXs

Earth Through the Eyes of NAPA-1: Commissioning Results and the Next Steps in CubeSat Earth Observation

Disruptive CubeSat technology has brought scientific missions within reach that were previously only achievable through larger spacecraft. Satellite Earth Observation is now the new frontier for governments, private industry, and academia. With the recent launch of the Napa-1 satellite the Royal Thai Airforce (RTAF) has joined the ranks by having its first ever Earth Observation CubeSat in space. Its design, launch, early operations (LEOPS), and commissioning have been carried out by ISISpace, supporting the market’s need for imagery from space. Napa-1, meaning firmament in Thai, is a 6U CubeSat with the Gecko Imager from SCS Space as its primary payload, capable of taking RGB snapshot images with a 39-meter ground sampling distance (GSD) from 500 km altitude. In addition, the TriScape camera from Simera Sense flies onboard as an in-orbit technology demonstrator and is capable of delivering high-quality images with a GSD of 5 meter in the RGB bands. With well over 200 images taken by the primary payload this paper will look back on this exciting first period of Napa-1’s operational life and proudly present the very first images taken by the satellite and the lessons learnt throughout this turnkey mission. With that many images taken and that much data generated, the implemented onboard- and on ground data handling systems have been put to the test. ISISpace has made use of KUBOS’ Major Tom for command and control and having integrated a low-level processing tool, also for image data preview and delivery. Insight is provided into the systems and tools in place for image target planning, image acquisition, satellite command and control, and data delivery to the customer. How is it ensured targets are successfully captured? How is the usefulness of the image data efficiently validated? Subsequently, how is knowledge transfer to the customer accomplished to ensure successful routine operations? ISISpace will share the valuable lessons learnt from the mission planning, data handling, operations, and training points of view and show relevant in-orbit data on, for example, attitude behavior and temperature. In parallel, ISISpace has taken the next step in CubeSat Earth observation by using Napa-1 as a baseline while accommodating larger data streams and leveraging a higher level of automation. Together with the companies Simera Sense and Pinkmatter Solutions, multispectral images with automated on ground data processing (L0 up to L3) are to be delivered by the follow-up mission, Napa-2, to be launched in the summer of 2021. Details on this mission, including a further outlook at how CubeSat imagery and on ground processing will be shaped in the next few years will be provided

Music therapy for depression.

Background Depression is a highly prevalent mood disorder that is characterised by persistent low mood, diminished interest, and loss of pleasure. Music therapy may be helpful in modulating moods and emotions. An update of the 2008 Cochrane review was needed to improve knowledge on effects of music therapy for depression. Objectives 1. To assess effects of music therapy for depression in people of any age compared with treatment as usual (TAU) and psychological, pharmacological, and/or other therapies. 2. To compare effects of different forms of music therapy for people of any age with a diagnosis of depression. Search methods We searched the following databases: the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR; from inception to 6 May 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; to 17 June 2016); Thomson Reuters/Web of Science (to 21 June 2016); Ebsco/PsycInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and PubMed (to 5 July 2016); the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, the National Guideline Clearing House, and OpenGrey (to 6 September 2016); and the Digital Access to Research Theses (DART)-Europe E-theses Portal, Open Access Theses and Dissertations, and ProQuest Dissertations and Theses Database (to 7 September 2016). We checked reference lists of retrieved articles and relevant systematic reviews and contacted trialists and subject experts for additional information when needed. We updated this search in August 2017 and placed potentially relevant studies in the "Awaiting classification" section; we will incorporate these into the next version of this review as appropriate

An Unusual Triad in Pediatric Neurology:A Case Report on Cerebral Palsy, Epilepsy, and Duchenne Muscular Dystrophy

We present a case of an unusual triad in pediatric neurology: a currently 12-year-old boy with cerebral palsy and epilepsy who was later also diagnosed with Duchenne muscular dystrophy. We describe the clinical path that resulted in this exceptional diagnosis. This case report illustrates how different neurological disorders may overshadow each other. In addition, it demonstrates that every child with cerebral palsy and either an atypical clinical course or with inexplicable laboratory values-as well as every infant boy born to a theoretical Duchenne muscular dystrophy carrier-should be subjected to additional investigations.</p