High-Throughput Phenotyping for Agronomic Traits in Cassava Using Aerial Imaging.

Large-scale phenotyping using unmanned aerial vehicles (UAVs) has been considered an important tool for plant selection. This study aimed to estimate the correlations between agronomic data and vegetation indices (VIs) obtained at different flight heights and to select prediction models to evaluate the potential use of aerial imaging in cassava breeding programs. Various VIs were obtained and analyzed using mixed models to derive the best linear unbiased predictors, heritability parameters, and correlations with various agronomic traits.

-Tosyl Hydrazone Benzopyran, a New Ligand of PPARα Obtained from Mapping the Conformational Space of Its Active Site.

We report here a new ligand for the peroxisome-proliferator-activated receptor type α (PPARα), an N-tosyl hydrazone benzopyran that was designed throughout the mapping of the polar zone of the binding site of PPARα; such a compound displays a strong activity on this receptor that is comparable to that of the reference compound WY-14643. For the design of the -tosyl hydrazone benzopyran, we have carried out an exhaustive conformational study of WY-14643 and a previously reported hydrazine benzopyran derivative using conformational potential energy surfaces (PES). This study allowed us to map in a systematic way the entire binding site of the PPARα.

Synthesis of a new 2-prenylated quinoline as potential drug for metabolic syndrome with pan-PPAR activity and anti-inflammatory effects.

We have previously reported the total synthesis and structure-activity relationships (SAR) of 2-prenylated benzopyrans with PPAR agonist activity. Herein, we have described the synthesis and PPAR activity of 2-prenylated benzopyrans and 2-prenylated quinolines. The benzopyran nucleus was generated via enamine-catalyzed Kabbe condensation, and the quinoline nucleus via Friedländer condensation.

Benzopyran hydrazones with dual PPARα/γ or PPARα/δ agonism and an anti-inflammatory effect on human THP-1 macrophages.

Peroxisome proliferator-activated receptors (PPARs) play a major role in regulating inflammatory processes, and dual or pan-PPAR agonists with PPARγ partial activation have been recognised to be useful to manage both metabolic syndrome and metabolic dysfunction-associated fatty liver disease (MAFLD). Previous works have demonstrated the capacity of 2-prenylated benzopyrans as PPAR ligands. Herein, we have replaced the isoprenoid bond by hydrazone, a highly attractive functional group in medicinal chemistry.

Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer.

Synthesis of three series of 2-aminopropyl derivatives containing a benzopyran nucleus was performed to evaluate their performance against triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-436) and normal breast epithelial cells (MCF10A). For the three series, the cytotoxic activity was as follows: -methylated derivatives (tertiary amines) 5b, 6b, and 7b > secondary amine benzopyrans 5, 6, and 7 > quaternary amine salts 5c, 6c, and 7c > free phenolic derivatives 5a, 6a, and 7a. The structure-activity relationship showed the importance of the presence of an amine group and a -fluorobenzyloxy substituent in the chromanol ring (IC values from 1.

New protocol for rapid cassava multiplication in field conditions: a perspective on speed breeding.

Despite the economic and social importance, high-yielding cassava cultivars are only released after extensive research, mainly due to the low multiplication rate. This study aimed to assess the impact of using smaller-sized seed cuttings treated with agrochemicals (8MP) compared to the conventional planting size (16 cm) on genetic parameters, agronomic performance, and the ranking of cassava clones based on yield and growth attributes. The evaluation was carried out in clonal evaluation trial (CET), preliminary yield trial (PYT), and uniform yield trials (UYT).

Development and validation of a hybrid immunoaffinity LC-MS/MS assay for quantitation of total antibody (TAb) from an antibody drug conjugate (ADC) PYX-201 in human plasma.

A hybrid immunoaffinity LC-MS/MS assay was developed and validated for the quantitation of total antibody (TAb) from an antibody drug conjugate (ADC) PYX-201 in human plasma. PYX-201 was proteolyzed using trypsin, and a characteristic peptide fragment PYX-201 P1 with ten amino acids IPPTFGQGTK from the complementarity-determining regions (CDRs) was used as a surrogate for the quantitation of the TAb from PYX-201. Stable isotope labelled (SIL) peptide I(C, N)PPTFG(C, N)QGTK was used as the internal standard (IS).

Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity.

Background And Purpose: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ activators have stimulated the development of novel pan-PPAR agonists to treat metabolic disorders. Here, we synthesized a new prenylated benzopyran (BP-2) and evaluated its PPAR-activating properties, anti-inflammatory effects and impact on metabolic derangements.

Experimental Approach: BP-2 was used in transactivation assays to evaluate its agonism to PPARα, PPARβ/δ and PPARγ.

Multiplex Hybrid Antigen-Capture LC-MRM Quantification in Sera and Nasal Lining Fluid of AZD7442, a SARS-CoV-2-Targeting Antibody Combination.

AZD7442 (tixagevimab [AZD8895]/cilgavimab [AZD1061]) is a monoclonal antibody (mAb) combination in development for the prevention and treatment of coronavirus disease 2019. Traditionally, bioanalysis of mAbs is performed using ligand binding assays (LBAs), which offer sensitivity, robustness, and ease of implementation. However, LBAs frequently require generation of critical reagents that typically take several months.

Synthesis and biological studies of "Polycerasoidol" and "trans-δ-Tocotrienolic acid" derivatives as PPARα and/or PPARγ agonists.

2-Prenylated benzopyrans represent a class of natural and synthetic compounds showing a wide range of significant activities. Polycerasoidol is a natural prenylated benzopyran isolated from the stem bark of Polyalthia cerasoides (Annonaceae) that exhibits dual PPARα/γ agonism and an anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium. Herein, we report the synthesis of three new series of prenylated benzopyrans containing one (series 1), two (series 2, "polycerasoidol" analogs) and three (series 3, "trans-δ-tocotrienolic acid" analogs) isoprenoid units in the hydrocarbon side chain at the 2-position of the chroman-6-ol (6-hydroxy-dihydrobenzopyran) scaffold.

Synthesis of 2-Prenylated Alkoxylated Benzopyrans by Horner-Wadsworth-Emmons Olefination with PPARα/γ Agonist Activity.

We have synthesized series of 2-prenylated benzopyrans as analogues of the natural polycerasoidol, a dual PPARα/γ agonist with anti-inflammatory effects. The prenylated side chain consists of five or nine carbons with an α-alkoxy-α,β-unsaturated ester moiety. Prenylation was introduced via the Grignard reaction, followed by Johnson-Claisen rearrangement, and the α-alkoxy-α,β-unsaturated ester moiety was introduced by the Horner-Wadsworth-Emmons reaction.

Regional heterogeneity of astrocyte morphogenesis dictated by the formin protein, Daam2, modifies circuit function.

Astrocytes display extraordinary morphological complexity that is essential to support brain circuit development and function. Formin proteins are key regulators of the cytoskeleton; however, their role in astrocyte morphogenesis across diverse brain regions and neural circuits is unknown. Here, we show that loss of the formin protein Daam2 in astrocytes increases morphological complexity in the cortex and olfactory bulb, but elicits opposing effects on astrocytic calcium dynamics.

First report of a subcutaneous infection by Cryptococcus neoformans (former Cryptococcus neoformans var. grubii) in a cat in Costa Rica.

This is a case report of a feline animal that presented with a skin infection on the neck from which Cryptococcus neoformans (former C. neoformans var. grubii) was isolated and identified.

Natural products and analogs as preventive agents for metabolic syndrome via peroxisome proliferator-activated receptors: An overview.

Natural products and synthetic analogs have drawn much attention as potential therapeutical drugs to treat metabolic syndrome. We reviewed the underlying mechanisms of 32 natural products and analogs with potential pharmacological effects in vitro, and especially in rodent models and/or patients, that usually act on the PPAR pathway, along with other molecular targets. Recent outstanding total syntheses or semisyntheses of these lead compounds are stated.

Consensus on the Treatment and Follow-Up for Metastatic Castration-Resistant Prostate Cancer: A Report From the First Global Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

Purpose: To present a summary of the recommendations for the treatment and follow-up for metastatic castration-resistant prostate cancer (mCRPC) as acquired through a questionnaire administered to 99 physicians working in the field of prostate cancer in developing countries who attended the Prostate Cancer Consensus Conference for Developing Countries.

Methods: A total of 106 questions out of more than 300 questions addressed the use of imaging in staging mCRPC, treatment recommendations across availability and response to prior drug treatments, appropriate drug treatments, and follow-up, and those same scenarios when limited resources needed to be considered. Responses were compiled and the percentages were presented by clinicians to support each response.

Daam2 couples translocation and clustering of Wnt receptor signalosomes through Rac1.

Wnt signaling plays a critical role in development across species and is dysregulated in a host of human diseases. A key step in signal transduction is the formation of Wnt receptor signalosomes, during which a large number of components translocate to the membrane, cluster together and amplify downstream signaling. However, the molecular processes that coordinate these events remain poorly defined.

Long-term ecological changes in fishes and macro-invertebrates in the world's warmest coral reefs.

The Arabian Gulf is a natural laboratory for examining the consequences of large-scale disturbances due to global warming on coral reef ecosystems because of its extreme temperature regime. Using a coral reef monitoring time series extending from 1985 to 2015, we examined the long-term ecological changes in fish and macro-invertebrate communities as these habitats suffered heat shocks. We used a GLMM modelling framework to obtain clean annual signals in community indicators from noisy data.

Regulation of Pv-specific interneurons in the medial prefrontal cortex and reward-seeking behaviors.

The corticostriatal circuitry and its glutamate-γ-aminobuturic acid (GABA) interactions play an essential role in regulating neuronal excitability during reward-seeking behavior. However, the contribution of GABAergic interneurons in the corticostriatal circuitry remains unclear. To investigate the role of GABAergic interneurons, we focused on parvalbumin-expressing fast-spiking interneurons (Pv-FSI) in the corticostriatal circuitry using the designer receptors exclusively activated by designer drugs approach in a Pv-Cre mouse model.

Multifaceted Bioanalytical Methods for the Comprehensive Pharmacokinetic and Catabolic Assessment of MEDI3726, an Anti-Prostate-Specific Membrane Antigen Pyrrolobenzodiazepine Antibody-Drug Conjugate.

Complex biotherapeutic modalities, such as antibody-drug conjugates (ADC), present significant challenges for the comprehensive bioanalytical characterization of their pharmacokinetics (PK) and catabolism in both preclinical and clinical settings. Thus, the bioanalytical strategy for ADCs must be designed to address the specific structural elements of the protein scaffold, linker, and warhead. A typical bioanalytical strategy for ADCs involves quantification of the Total ADC, Total IgG, and Free Warhead concentrations.

Acetogenins from Annonaceae family. Their potential biological applications.

The aim of this contribution has been to continue with the knowledge about newly isolated acetogenins from Annonaceae family for the last fifteen years. This review will report classification, extraction, isolation, elucidation of the structure, biological activities and mechanism of action of such interesting natural products. In fact, out of the 532 compounds reviewed, 115 previously non-described annonaceous acetogenins have been added to the list of isolated compounds from 2005 to May 2019.

A novel seed treatment-based multiplication approach for cassava planting material.

Cassava (Manihot esculenta Crantz) is an important food security crop in many parts of the developing world. The crop's high yield potential and multitude of uses-both for nutrition and processing-render cassava a promising driver for the development of rural value chains. It is traditionally propagated from stem cuttings of up to 30 cm in length, giving a multiplication rate as low as 1:10.

1-(2'-Bromobenzyl)-6,7-dihydroxy--methyl-tetrahydroisoquinoline and 1,2-Demethyl-nuciferine as Agonists in Human D Dopamine Receptors.

Certain D-like dopamine receptor (DR) agonists are useful therapeutically as antiparkinsonian drugs, whereas D-like DR antagonists or partial agonists are proven effective as antipsychotics. Two isoquinoline derivatives, 1-(2'-bromobenzyl)-6,7-dihydroxy--methyl-tetrahydroisoquinoline (Br-BTHIQ, ) and 1,2-demethyl-nuciferine (aporphine, ), were herein synthesized, and their dopaminergic affinity in cloned human DR, DR, and DR subtypes and their behavior as agonists/antagonists were evaluated. They showed affinity values () for hD, hD, and hD DR within the nanomolar range.

Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators.

We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski's rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucleus) by benzopyran-4-one, dihydrobenzopyran or benzopyran-4-ol; (ii) the side chain at 2-position by shortening to C3, C4 and C5-carbons versus C-9-carbons of polycerasoidol; (iii) the carboxylic group (polar head) by oxygenated groups (hydroxyl, acetoxy, epoxide, ester, aldehyde) or non-oxygenated motifs (allyl and alkyl). Benzopyran-4-ones 6, 12, 13 and 17 as well as dihydrobenzopyrans 22, 24 and 25 were able to activate hPPARα, whereas benzopyran-4-one (7) with C5-carbons in the side chain exhibited hPPARγ agonism.

Immunoaffinity LC-MS/MS to quantify a PEGylated anti-Factor D Fab biotherapeutic in cynomolgus monkey serum.

To develop a sensitive hybrid immunoaffinity LC-MS/MS monkey serum assay to quantify multiple components of anti-Factor D; a complex PEGylated Fab biotherapeutic explored as a therapy for age-related macular degeneration. Immunoaffinity enrichment of PEGylated anti-Factor D Fab, including fully conjugated, partially conjugated and unconjugated (i.e.