African agri-entrepreneurship in the face of the COVID-19 pandemic.

Background: The African continent is known for high entrepreneurial activity, especially in the agricultural sector. Despite this, the continent's economic development is below expectations, due to numerous factors constraining the growth and sustainability of agricultural SMEs. These constraints have been exacerbated by the COVID-19 pandemic.

Developing Telemedicine Curriculum Competencies for Graduate Medical Education: Outcomes of a Modified Delphi Process.

Purpose: Telemedical applications have only recently begun to coalesce into the field of telemedicine due to varying definitions of telemedicine and issues around reimbursement. This process has been accelerated by the COVID-19 pandemic and the ensuing expansion of telemedicine delivery. This article demonstrates the development of a set of proposed competencies for a telemedicine curriculum in graduate medical education.

Preparing for the Second Surge: Preventing Posttraumatic Stress Disorder and Building Resilience for Health Care Workers in the Face of COVID-19.

The global community needs to be aware of the potential psychosocial consequences that may be experienced by health care workers who are actively managing patients with coronavirus disease (COVID-19). These health care workers are at increased risk for experiencing mood and trauma-related disorders, including posttraumatic stress disorder (PTSD). In this concept article, strategies are recommended for individual health care workers and hospital leadership to aid in mitigating the risk of PTSD, as well as to build resilience in light of a potential second surge of COVID-19.

Practical Solutions for Healthcare Worker Protection During the COVID-19 Pandemic Response in the Ambulatory, Emergency, and Inpatient Settings.

Objective: Protecting healthcare workers is an essential component of a successful response to the COVID-19 pandemic. The resource intensive nature of infectious disease protection, budgetary constraints, and global shortages of personal protective equipment (PPE) make this a daunting task. Practical, easily implemented strategies for healthcare workers (HCW) protection are needed.

Allocation of Scarce Resources in a Pandemic: A Systematic Review of US State Crisis Standards of Care Documents.

The aim of this systematic review was to locate and analyze United States state crisis standards of care (CSC) documents to determine their prevalence and quality. Following PRISMA guidelines, Google search for "allocation of scarce resources" and "crisis standards of care (CSC)" for each state. We analyzed the plans based on the 2009 Institute of Medicine (IOM) report, which provided guidance for establishing CSC for use in disaster situations, as well as the 2014 CHEST consensus statement's 11 core topic areas.

Nitroalkanes as Versatile Nucleophiles for Enzymatic Synthesis of Noncanonical Amino Acids.

C-C bond-forming reactions often require nucleophilic carbon species rarely compatible with aqueous reaction media, thus restricting their appearance in biocatalysis. Here we report the use of nitroalkanes as a structurally versatile class of nucleophilic substrates for C-C bond formation catalyzed by variants of the β-subunit of tryptophan synthase (TrpB). The enzymes accept a wide range of nitroalkanes to form noncanonical amino acids, here the nitro group can serve as a handle for further modification.

The impact of ICT-enabled extension campaign on farmers' knowledge and management of fall armyworm in Uganda.

This study evaluates the unique and combined effects of three complementary ICT-based extension methods - interactive radio, mobile SMS messages and village-based video screenings - on farmers' knowledge and management of fall armyworm (FAW), an invasive pest of maize that is threatening food security in sub-Saharan Africa and Asia. Building on a survey of maize farmers in western Uganda and using various selection-on-observables estimators, we find consistent evidence that participation in the ICT-based extension campaigns significantly increases farmers' knowledge about FAW and stimulates the adoption of agricultural technologies and practices for the management of the pest. We also show that exposure to multiple campaign channels yields significantly higher outcomes than exposure to a single channel, with some evidence of additive effects.

Impact Assessment of Biological Control-Based Integrated Pest Management in Rice and Maize in the Greater Mekong Subregion.

The impact and sustainability of two interventions that have been formulated to introduce integrated pest management (IPM) into rice and maize crops in Southwestern China, Laos, and Myanmar between 2011 and 2016, and were assessed at the end of 2017. From 22 rearing facilities established during the interventions, 11 were still producing substantial quantities of biocontrol agents 1.5 years after project support had ended, while seven had stopped operations completely, and four were doing stock rearing only.

Improved Synthesis of 4-Cyanotryptophan and Other Tryptophan Analogues in Aqueous Solvent Using Variants of TrpB from Thermotoga maritima.

The use of enzymes has become increasingly widespread in synthesis as chemists strive to reduce their reliance on organic solvents in favor of more environmentally benign aqueous media. With this in mind, we previously endeavored to engineer the tryptophan synthase β-subunit (TrpB) for production of noncanonical amino acids that had previously been synthesized through multistep routes involving water-sensitive reagents. This enzymatic platform proved effective for the synthesis of analogues of the amino acid tryptophan (Trp), which are frequently used in pharmaceutical synthesis as well as chemical biology.

Enantioselective Total Synthesis of Nigelladine A via Late-Stage C-H Oxidation Enabled by an Engineered P450 Enzyme.

An enantioselective total synthesis of the norditerpenoid alkaloid nigelladine A is described. Strategically, the synthesis relies on a late-stage C-H oxidation of an advanced intermediate. While traditional chemical methods failed to deliver the desired outcome, an engineered cytochrome P450 enzyme was employed to effect a chemo- and regioselective allylic C-H oxidation in the presence of four oxidizable positions.

Unlocking Reactivity of TrpB: A General Biocatalytic Platform for Synthesis of Tryptophan Analogues.

Derivatives of the amino acid tryptophan (Trp) serve as precursors for the chemical and biological synthesis of complex molecules with a wide range of biological properties. Trp analogues are also valuable as building blocks for medicinal chemistry and as tools for chemical biology. While the enantioselective synthesis of Trp analogues is often lengthy and requires the use of protecting groups, enzymes have the potential to synthesize such products in fewer steps and with the pristine chemo- and stereoselectivity that is a hallmark of biocatalysis.

Aspartyl Oxidation Catalysts That Dial In Functional Group Selectivity, along with Regio- and Stereoselectivity.

A remarkable aspect of enzyme evolution is the portability of catalytic mechanisms for fundamentally different chemical reactions. For example, aspartyl proteases, which contain two active site carboxylic acid groups, catalyze the hydrolysis of amide bonds, while glycosyltransferases (and glycosyl hydrolases), which often also contain two active site carboxylates, have evolved to form (or break) glycosidic bonds. However, neither catalyst exhibits cross-reactivity in the intracellular environment.

A Panel of TrpB Biocatalysts Derived from Tryptophan Synthase through the Transfer of Mutations that Mimic Allosteric Activation.

Naturally occurring enzyme homologues often display highly divergent activity with non-natural substrates. Exploiting this diversity with enzymes engineered for new or altered function, however, is laborious because the engineering must be replicated for each homologue. A small set of mutations of the tryptophan synthase β-subunit (TrpB) from Pyrococcus furiosus, which mimics the activation afforded by binding of the α-subunit, was demonstrated to have a similar activating effect in different TrpB homologues with as little as 57 % sequence identity.

Synthesis of β-Branched Tryptophan Analogues Using an Engineered Subunit of Tryptophan Synthase.

We report that l-threonine may substitute for l-serine in the β-substitution reaction of an engineered subunit of tryptophan synthase from Pyrococcus furiosus, yielding (2S,3S)-β-methyltryptophan (β-MeTrp) in a single step. The trace activity of the wild-type β-subunit on this substrate was enhanced more than 1000-fold by directed evolution. Structural and spectroscopic data indicate that this increase is correlated with stabilization of the electrophilic aminoacrylate intermediate.

Directed evolution of the tryptophan synthase β-subunit for stand-alone function recapitulates allosteric activation.

Enzymes in heteromeric, allosterically regulated complexes catalyze a rich array of chemical reactions. Separating the subunits of such complexes, however, often severely attenuates their catalytic activities, because they can no longer be activated by their protein partners. We used directed evolution to explore allosteric regulation as a source of latent catalytic potential using the β-subunit of tryptophan synthase from Pyrococcus furiosus (PfTrpB).

A Synergistic Combinatorial and Chiroptical Study of Peptide Catalysts for Asymmetric Baeyer-Villiger Oxidation.

We report an approach to the asymmetric Baeyer-Villiger oxidation utilizing bioinformatics-inspired combinatorial screening for catalyst discovery. Scaled-up validation of our on-bead efforts with a circular dichroism-based assay of alcohols derived from the products of solution-phase reactions established the absolute configuration of lactone products; this assay proved equivalent to HPLC in its ability to evaluate catalyst performance, but was far superior in its speed of analysis. Further solution-phase screening of a focused library suggested a mode of asymmetric induction that draws distinct parallels with the mechanism of Baeyer-Villiger monooxygenases.

Catalyst control over regio- and enantioselectivity in Baeyer-Villiger oxidations of functionalized ketones.

We report a peptide-based catalyst that can strongly influence the regio- and enantioselectivity of the Baeyer-Villiger (BV) oxidation of cyclic ketones bearing amide, urea, or sulfonamide functional groups. Both types of selectivity are thought to arise from a catalyst-substrate hydrogen-bonding interaction. Furthermore, in selected cases, the reactions exhibit the hallmarks of parallel kinetic resolution.

Total synthesis and isolation of citrinalin and cyclopiamine congeners.

Many natural products that contain basic nitrogen atoms--for example alkaloids like morphine and quinine-have the potential to treat a broad range of human diseases. However, the presence of a nitrogen atom in a target molecule can complicate its chemical synthesis because of the basicity of nitrogen atoms and their susceptibility to oxidation. Obtaining such compounds by chemical synthesis can be further complicated by the presence of multiple nitrogen atoms, but it can be done by the selective introduction and removal of functional groups that mitigate basicity.

A peptide-embedded trifluoromethyl ketone catalyst for enantioselective epoxidation.

The development of peptide-based oxidation catalysts that use a transiently generated dioxirane as the chemically active species is reported. The active catalyst is a chiral trifluoromethyl ketone (Tfk) with a pendant carboxylic acid that can be readily incorporated into a peptide. These peptides were capable of epoxidizing alkenes in high yield (up to 89%) and enantiomeric ratios (er) ranging from 69.

¹³C magnetic resonance spectroscopy detection of changes in serine isotopomers reflects changes in mitochondrial redox status.

The glycine cleavage system (GCS), the major pathway of glycine catabolism in liver, is found only in the mitochondria matrix and is regulated by the oxidized nicotinamide adenine dinucleotide (NAD(+) )/reduced nicotinamide adenine dinucleotide (NADH) ratio. In conjunction with serine hydroxymethyltransferase, glycine forms the 1 and 2 positions of serine, while the 3 position is formed exclusively by GCS. Therefore, we sought to exploit this pathway to show that quantitative measurements of serine isotopomers in liver can be used to monitor the NAD(+) /NADH ratio using (13) C NMR spectroscopy.

Preoperative chemoradiation for rectal cancer using capecitabine and celecoxib correlated with posttreatment assessment of thymidylate synthase and thymidine phosphorylase expression.

Purpose: Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy. The toxicity, efficacy, surgical morbidity, and immunohistochemical TS and TP expression were assessed in surgical resection specimens after preoperative chemoradiation.

Methods And Materials: Twenty patients with clinical stage I to III rectal adenocarcinoma received preoperative chemoradiation and underwent surgical resection 6 weeks later.

Linking international agricultural research knowledge with action for sustainable development.

We applied an innovation framework to sustainable livestock development research projects in Africa and Asia. The focus of these projects ranged from pastoral systems to poverty and ecosystems services mapping to market access by the poor to fodder and natural resource management to livestock parasite drug resistance. We found that these projects closed gaps between knowledge and action by combining different kinds of knowledge, learning, and boundary spanning approaches; by providing all partners with the same opportunities; and by building the capacity of all partners to innovate and communicate.