Drug discovery research in Ghana, challenges, current efforts, and the way forward

We have a long-term vision to develop drug discovery research capacity within Ghana, to tackle unmet medical needs in Ghana and the wider West African region. However, there are several issues and challenges that need to be overcome to enable this vision, including training, human resource, equipment, infrastructure, procurement, and logistics. We discuss these challenges from the context of Ghana in this review. An important development is the universities and research centres within Ghana working together to address some of these challenges. Therefore, while there is a long way to go to fully accomplish our vision, there are encouraging signs

Mechanismus der mRNA Lokalisation in Xenopus Oozyten

Der gerichtete Transport spezifischer mRNAs ist ein Mechanismus zur Herstellung von Asymmetrie, welche eine wichtige biologische Rolle spielt. In Xenopus Oozyten ist die Lokalisierung von mRNA zum vegetativen Kortex sowohl für die Bildung der Keimblätter als auch die Entwicklung der Keimzellen bedeutsam. Mittels einer biochemischen Aufreinigungsstrategie, die auf der Anreicherung von RNPs aufgrund ihrer Größe basiert, wurden Xenopus Elr-Proteine, Homologe der Hu/ELAV-Proteinfamilie, welche in vier Isoformen vorliegen, als Komponenten der vegetativen mRNA-Lokalisationsmaschinerie identifiziert.Diese Proteine binden spezifisch an die Lokalisationselemente verschiedener Xenopus mRNAs aller drei Lokalisationswege. Außerdem sind sie gemeinsam mit anderen Lokalisationsproteinen, wie Vg1RBP, XStaufen1, VgRBP60 und 40LoVe Teil eines Ribonukleoprotein-Partikels (RNP). Immunopräzipitierte ElrA/B-RNPs enthalten andere interessante, neue Komponenten lokalisierter RNPs, wie z.B. RAP42/46, XhermesR und SLBP2. Zusätzlich wurden maternale mRNA-maskierende Proteine, nämlich FRGY2a/b und Xp54 identifiziert. Dies deutet auf eine Maskierung lokalisierter mRNAs hin.Elr-Proteine binden stark an die lokalisierende XDead End (XDE)-mRNA. Die Blockierung dieser Bindung durch Mutagenese des Lokalisationselementes oder durch maskierende antisense Morpholino-Oligonukleotide inhibiert die vegetative Lokalisierung dieser mRNA in Xenopus Oozyten. ElrA/B-Proteine liegen hauptsächlich zytoplasmatisch vor, wobei ElrA auch schwach im Nukleus lokalisiert ist. Möglicherweise wird es bereits im Kern Teil des RNPs. Ebenso wie andere bekannte Lokalisationsproteine sind ElrA/B außerdem am vegetativen Kortex angereichert.Weiterhin wurde festgestellt, dass ElrA/B-Proteine die Translation in Xenopus Oozyten leicht aktivieren, wenn sie an die 3 UTR einer Reporter rekrutiert werden. Vergleicht man allerdings die Translationsrate von Reporter-mRNAs, welche das ElrA/B-bindende XDE LE enthalten, mit Reportern, in denen die Bindung durch Mutationen blockiert ist, kann kein signifikanter Unterschied festgestellt werden. Weitere Analysen zeigten außerdem, dass die Bindung von ElrA/B an das XDE LE hat keinen signifikanten Einfluß auf die mRNA-Stabilität in der Oozyte. Allerdings zeigen die mutierten XDE LE-Fragmente eine verringerte Stabilität in den primordialen Keinzellen

Codeine dysregulates ribosome biogenesis in Escherichia coli with DNA double-strand breaks to chart path to new classes of antibiotics

Aim: A bacterial genetics-guided approach was utilized for the discovery of new compounds affecting bacterial genome stability. Materials & methods: Fungal extracts and fractions were tested for genome instability-mediated antibacterial activity. Interaction assays and RT-qPCR were used to identify compounds that boost the activity of sub-minimum inhibitory concentration streptomycin and obtain insights on the molecular mechanisms of the primary hit compound, respectively. Results: Several extracts and fractions caused bacterial genome instability. Codeine, in synergy with streptomycin, regulates double-strand break (DSB) repair and causes bacterial ribosome dysfunction in the absence of DSBs, and dysregulation of ribosome biogenesis in a DSB-dependent manner. Conclusion: This study demonstrates a potential viable strategy that we are exploring for the discovery of new chemical entities with activities against Escherichia coli and other bacterial pathogens

Electrochemical Response of <i>Saccharomyces cerevisiae</i> Corresponds to Cell Viability upon Exposure to <i>Dioclea reflexa</i> Seed Extracts and Antifungal Drugs

Dioclea reflexa bioactive compounds have been shown to contain antioxidant properties. The extracts from the same plant are used in traditional medical practices to treat various diseases with impressive outcomes. In this study, ionic mobility in Saccharomyces cerevisiae cells in the presence of D. reflexa seed extracts was monitored using electrochemical detection methods to link cell death to ionic imbalance. Cells treated with ethanol, methanol, and water extracts were studied using cyclic voltammetry and cell counting to correlate electrochemical behavior and cell viability, respectively. The results were compared with cells treated with pore-forming Amphotericin b (Amp b), as well as Fluconazole (Flu) and the antimicrobial drug Rifampicin (Rif). The D. reflexa seed water extract (SWE) revealed higher anodic peak current with 58% cell death. Seed methanol extract (SME) and seed ethanol extract (SEE) recorded 31% and 22% cell death, respectively. Among the three control drugs, Flu revealed the highest cell death of about 64%, whereas Amp b and Rif exhibited cell deaths of 35% and 16%, respectively, after 8 h of cell growth. It was observed that similar to SWE, there was an increase in the anodic peak current in the presence of different concentrations of Amp b, which also correlated with enhanced cell death. It was concluded from this observation that Amp b and SWE might follow similar mechanisms to inhibit cell growth. Thus, the individual bioactive compounds from the water extracts of D. reflexa seeds could further be purified and tested to validate their potential therapeutic application. The strategy to link electrochemical behavior to biochemical responses could be a simple, fast, and robust screening technique for new drug targets and to understand the mechanism of action of such drugs against disease models

Supplementary material: Codeine dysregulates ribosome biogenesis in Escherichia coli with DNA double-strand breaks to chart path to new classes of antibiotics.docx

Supplementary Information</p

Science NextGen Voices: Science-inspired sustainable behavior.

We asked young scientists this question: How has your awareness of science inspired you to adopt more sustainable and environmentally friendly behavior? Respondents from around the world described scientific concepts, images, and research from a range of fields that inspire them to make environmentally friendly decisions and model sustainable behavior for others, in both their personal and professional lives. Read a selection of the best responses here. Follow NextGen on Twitter with hashtag #NextGenSci

Education for the future.

We asked young scientists: Are our schools and universities adequately prepared to educate young people for future challenges? What is the most pressing issue in your field, and what one improvement could your country make to its current education system to prepare students to face it? The responses expressed concerns about the current state of education in countries around the world. Many students lack access to the information they need, and those with access are often constrained by curriculum that emphasizes rote learning and isolated subjects. Our respondents suggested a variety of improvements to prepare the next generation for success

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4&nbsp;% presented with RS, while 13.6&nbsp;% had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7&nbsp;% vs RS: 37.5&nbsp;%). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1&nbsp;% vs. RS 32.0&nbsp;%), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders