Selective Chirality-Driven Photopolymerization of Diacetylene Crystals.

Crystal engineering of two diacetylene monomers was achieved by branching two chiral groups [R = PhC*MeNH(CO)CH] exhibiting an enantiopure configuration of ,-() and an achiral ,--isomer (). The X-ray structures of and reveal the presence of supramolecular arrangements driven by intermolecular H-bonding. A significant intermolecular closer proximity in than that in is depicted, ultimately resulting in a slow thermal (days) and swift (min) photochemical polymerization of to form , whereas is unreactive.

High throughput screening for drugs that inhibit 3C-like protease in SARS-CoV-2.

The SARS coronavirus 2 (SARS-CoV-2) pandemic remains a major problem in many parts of the world and infection rates remain at extremely high levels. This high prevalence drives the continued emergence of new variants, and possibly ones that are more vaccine-resistant and that can drive infections even in highly vaccinated populations. The high rate of variant evolution makes clear the need for new therapeutics that can be clinically applied to minimize or eliminate the effects of COVID-19.

Crystal Structures of Lignocellulosic Furfuryl Biobased Polydiacetylenes with Hydrogen-Bond Networks: Influencing the Direction of Solid-State Polymerization through Modification of the Spacer Length.

We present the topochemical polymerization of two lignocellulosic biobased diacetylenes (DAs) that only differ by an alkyl spacer length of 1 methylene ( = 1) or 3 methylene units ( = 3) between the diyne and carbamate functionalities. Their crystalline molecular organizations have the distinctive feature of being suitable for polymerization in two potential directions, either parallel or skewed to the hydrogen-bonded (HB) network. However, single-crystal structures of the final polydiacetylenes (PDAs) demonstrate that the resulting orientation of the conjugated backbones is different for these two derivatives, which lead to HB supramolecular polymer networks (2D nanosheets) for = 1 and to independent linear PDA chains with intramolecular HBs for = 3.

High throughput screening for compounds to the orphan nuclear receptor NR2F6.

NR2F6 is considered an orphan nuclear receptor since its endogenous ligand has yet to be identified. Recently, NR2F6 has emerged as a novel cancer therapeutic target. NR2F6 has been demonstrated to be upregulated or overexpressed in several cancers.

Lead identification using 3D models of pancreatic cancer.

Recent technological advances have enabled 3D tissue culture models for fast and affordable HTS. We are no longer bound to 2D models for anti-cancer agent discovery, and it is clear that 3D tumor models provide more predictive data for translation of preclinical studies. In a previous study, we validated a microplate 3D spheroid-based technology for its compatibility with HTS automation.

Screening for modulators of autism spectrum disorder using induced human neurons.

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder. There are no drugs to treat the core symptoms. De novo mutations often play an important role in ASD and multiple high-risk loci have been identified in the last decade.

Rapid deployment of inexpensive open-source orbital shakers in support of high-throughput screening.

Open-source projects continue to grow in popularity alongside open-source educational resources, software, and hardware tools. The impact of this increased availability of open-source technologies is that end users are empowered to have greater control over the tools that they work with. This trend extends in the life science laboratory space, where new open-source projects are routinely being published that allow users to build and modify scientific equipment specifically tailored to their needs, often at a reduced cost from equivalent commercial offerings.

Identification of potent small molecule inhibitors of SARS-CoV-2 entry.

The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells.

High-Throughput Screening for Drugs That Inhibit Papain-Like Protease in SARS-CoV-2.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 has triggered an ongoing global pandemic whereby infection may result in a lethal severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, millions of confirmed cases and hundreds of thousands of deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. The purported development of a vaccine could require at least 1-4 years, while the typical timeline from hit finding to drug registration of an antiviral is >10 years.

Validation of serum gamma-glutamyl transferase activity and body weight information for identifying dairy calves that are too young to be transported to auction markets in Canada.

Dairy calves are at risk of being stressed when transported during the first week of life. A new Canadian federal rule will forbid transportation of calves younger than 9 d old to auction market. However, in the absence of reliable information to determine birth date, other indirect methods would be of interest.

Applications for Open Source Microplate-Compatible Illumination Panels.

Microplates are commonly used in the modern laboratory environment for a wide variety of tasks both in small-scale laboratory benchtop operations as well as large-scale high-throughput screening (HTS) campaigns. Though laboratory automation has greatly increased the utility of microplates there remain instances where automation-based instrumentation is not feasible, cost-effective or compatible with microplate formatting needs. In these cases, microplates must be manually prepared.

Automating a Magnetic 3D Spheroid Model Technology for High-Throughput Screening.

Affordable and physiologically relevant three-dimensional (3D) cell-based assays used in high-throughput screening (HTS) are on the rise in early drug discovery. These technologies have been aided by the recent adaptation of novel microplate treatments and spheroid culturing techniques. One such technology involves the use of nanoparticle (NanoShuttle-PL) labeled cells and custom magnetic drives to assist in cell aggregation to ensure rapid 3D structure formation after the cells have been dispensed into microtiter plates.

Design of Microplate-Compatible Illumination Panels for a Semiautomated Benchtop Pipetting System.

Microplates are an essential tool used in laboratories for storing research materials and performing assays. Many types of laboratory automation exist that greatly reduce the effort needed to utilize microplates; however, there are cases where the use of such automation is not feasible or practical. In these instances, researchers must work in an environment where liquid handling operations are performed manually with handheld pipetting devices.

The Scripps Molecular Screening Center and Translational Research Institute.

The Scripps Research Molecular Screening Center (SRMSC) was founded in 2004 and comprises more than $22 million of specialized automation. As part of the Translational Research Institute (TRI), it comprises early drug discovery labs and medicinal chemistry. Together with Scripps Research at the La Jolla, California, campus, this represents one of the most competitive academic industrial screening centers worldwide.

IoT for Real-Time Measurement of High-Throughput Liquid Dispensing in Laboratory Environments.

Critical to maintaining quality control in high-throughput screening is the need for constant monitoring of liquid-dispensing fidelity. Traditional methods involve operator intervention with gravimetric analysis to monitor the gross accuracy of full plate dispenses, visual verification of contents, or dedicated weigh stations on screening platforms that introduce potential bottlenecks and increase the plate-processing cycle time. We present a unique solution using open-source hardware, software, and 3D printing to automate dispenser accuracy determination by providing real-time dispense weight measurements via a network-connected precision balance.

Improved Scalability of Neuron-Based Phenotypic Screening Assays for Therapeutic Discovery in Neuropsychiatric Disorders.

There is a pressing need to improve approaches for drug discovery related to neuropsychiatric disorders (NSDs). Therapeutic discovery in neuropsychiatric disorders would benefit from screening assays that can measure changes in complex phenotypes linked to disease mechanisms. However, traditional assays that track complex neuronal phenotypes, such as neuronal connectivity, exhibit poor scalability and are not compatible with high-throughput screening (HTS) procedures.

A Homogeneous Cell-Based Halide-Sensitive Yellow Fluorescence Protein Assay to Identify Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator Ion Channel.

Cystic fibrosis (CF), an inherited genetic disease, is caused by mutation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes an ion channel involved in hydration maintenance by anion homeostasis. Ninety percent of CF patients possess one or more copies of the F508del CFTR mutation. This mutation disrupts trafficking of the protein to the plasma membrane and diminishes function of mature CFTR.

Isomorphous crystal structures of chlorodi-acetyl-ene and iododi-acetyl-ene derivatives: simultaneous hydrogen and halogen bonds on carbon-yl.

The crystal structures of -butyl (5-chloro-penta-2,4-diyn-1-yl)carbamate, CHClNO (), and -butyl (5-iodo-penta-2,4-diyn-1-yl)carbamate, CHINO (), are isomorphous to previously reported structures and accordingly their mol-ecular and supra-molecular structures are similar. In the crystals of () and (), mol-ecules are linked into very similar two-dimensional wall organizations with anti-parallel carbamate groups involved in a combination of hydrogen and halogen bonds (bifurcated N-H⋯O=C and C≡C-⋯O=C inter-actions on the same carbonyl group). There is no long-range parallel stacking of diynes, so the topochemical polymerization of di-acetyl-ene is prevented.

Determining bovine viral diarrhea and infectious bovine rhinotracheitis infections in dairy cattle using precolostral blood.

The objective of this study was to determine if precolostral blood samples are useful to detect apparent fetal infections with bovine viral diarrhea (BVD) and infectious bovine rhinotracheitis (IBR) viruses. A convenience sample of 317 sera from 50 Canadian herds was used in the study. Antibody level was measured using 2 commercial IBR and BVD ELISA kits.

The histomorphologic spectrum of primary cutaneous diffuse large B-cell lymphoma: a study of 79 cases.

Primary cutaneous large B-cell lymphomas (PCLBCL) have historically been a matter of debate in the literature. The 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification scheme segregated cutaneous B-cell lymphomas into 3 groups: primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center cell lymphoma, and primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), "leg type" (PCDLBCL-LT). Additionally, the WHO-EORTC classification scheme utilized the term PCLBCL "other" not otherwise specified (NOS) type for rare cases of PCLBCL not belonging to either the "leg type" or the primary cutaneous follicle center cell lymphoma group.

Monitoring of HTS compound library quality via a high-resolution image acquisition and processing instrument.

This report presents the high-resolution image acquisition and processing instrument for compound management applications (HIAPI-CM). The HIAPI-CM combines imaging spectroscopy and machine-vision analysis to perform rapid assessment of high-throughput screening (HTS) compound library quality. It has been customized to detect and classify typical artifacts found in HTS compound library microtiter plates (MTPs).

Association of BoLA DRB3 and DQA1 alleles with susceptibility to Neospora caninum and reproductive outcome in Quebec Holstein cattle.

The BoLA DRB3 and DQA1 genes are part of the major histocompatibility complex (MHC) class II in cattle. These genes are highly polymorphic and have been associated with resistance to several diseases, such as mastitis, Bovine Leukemia Virus (BLV) and dermatophilis. Sequenced based typing of these genes has been carried out extensively from blood samples; however it is often impractical or expensive to obtain such samples.