Retrospective SARS-CoV-2 human antibody development trajectories are largely sparse and permissive.

Immunological interventions, like vaccinations, are enabled by the predictive control of humoral responses to novel antigens. While the development trajectories for many broadly neutralizing antibodies (bnAbs) have been measured, it is less established how human subtype-specific antibodies develop from their precursors. In this work, we evaluated the retrospective development trajectories for eight anti-SARS-CoV-2 Spike human antibodies (Abs).

Large-scale and long-term wildlife research and monitoring using camera traps: a continental synthesis.

Camera traps are widely used in wildlife research and monitoring, so it is imperative to understand their strengths, limitations, and potential for increasing impact. We investigated a decade of use of wildlife cameras (2012-2022) with a case study on Australian terrestrial vertebrates using a multifaceted approach. We (i) synthesised information from a literature review; (ii) conducted an online questionnaire of 132 professionals; (iii) hosted an in-person workshop of 28 leading experts representing academia, non-governmental organisations (NGOs), and government; and (iv) mapped camera trap usage based on all sources.

Ethnicity does not change burn resuscitation and time to first excision.

Health and racial disparities can limit access to preventative, trauma, and chronic disease care but have not been addressed in burn resuscitation. Over- and under-resuscitation contribute to increased overall hospital costs, and morbidity and mortality rates. The primary objective of this study was to identify potential racial disparities that may exist during the initial fluid resuscitation after burn injury.

Pamidronate for Hypercalcemia in Critically Ill Surgical Patients.

Introduction: Hypercalcemia in critically ill patients is associated with an increased severity of illness and mortality that becomes worse as the levels rise. Pamidronate was evaluated for the treatment of hypercalcemia in critically ill surgical patients.

Methods: This retrospective study evaluated 30 critically ill surgical patients who developed hypercalcemia (ionized calcium (iCa)≥1.

Genetic mapping of QTLs for resistance to bacterial leaf streak in hexaploid wheat.

Robust QTLs conferring resistance to bacterial leaf streak in wheat were mapped on chromosomes 3B and 5A from the variety Boost and on chromosome 7D from the synthetic wheat line W-7984. Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa poses a significant threat to global wheat production.

Evaluation of durum and hard red spring wheat panels for sensitivity to necrotrophic effectors produced by .

Septoria nodorum blotch is an important disease of both durum and hard red spring wheat (HRSW) worldwide. The disease is caused by the necrotrophic fungal pathogen Parastagonospora nodorum when compatible gene-for-gene interactions occur between pathogen-produced necrotrophic effectors (NEs) and corresponding host sensitivity genes. To date, nine sensitivity gene-NE interactions have been identified, but there is little information available regarding their overall frequency in durum and HRSW.

Chromatographic Determination of Permeability-Relevant Lipophilicity Facilitates Rapid Analysis of Macrocyclic Peptide Scaffolds.

Hydrocarbon-determined shake-flask measurements have demonstrated great utility for optimizing lipophilicity during early drug discovery. Alternatively, chromatographic methods confer reduced experimental error and improved handling of complex mixtures. In this study, we developed a chromatographic approach for estimating hydrocarbon-water shake-flask partition coefficients for a variety of macrocyclic peptides and other bRo5 molecules including PROTACs.

Association mapping of tan spot and septoria nodorum blotch resistance in cultivated emmer wheat.

A total of 65 SNPs associated with resistance to tan spot and septoria nodorum blotch were identified in a panel of 180 cultivated emmer accessions through association mapping Tan spot and septoria nodorum blotch (SNB) are foliar diseases caused by the respective fungal pathogens Pyrenophora tritici-repentis and Parastagonospora nodorum that affect global wheat production. To find new sources of resistance, we evaluated a panel of 180 cultivated emmer wheat (Triticum turgidum ssp. dicoccum) accessions for reactions to four P.

Evolution, diversity, and function of the disease susceptibility gene Snn1 in wheat.

Septoria nodorum blotch (SNB), caused by Parastagonospora nodorum, is a disease of durum and common wheat initiated by the recognition of pathogen-produced necrotrophic effectors (NEs) by specific wheat genes. The wheat gene Snn1 was previously cloned, and it encodes a wall-associated kinase that directly interacts with the NE SnTox1 leading to programmed cell death and ultimately the development of SNB. Here, sequence analysis of Snn1 from 114 accessions including diploid, tetraploid, and hexaploid wheat species revealed that some wheat lines possess two copies of Snn1 (designated Snn1-B1 and Snn1-B2) approximately 120 kb apart.

Skeletal muscle architecture and aging: A comparison of ultrasound techniques and an assessment of intrarater reliability.

Objective: To assess intrarater reliability of ultrasound-determined measurements of skeletal muscle characteristics across different measurement outcomes, imaging techniques, and age groups.

Methods: 2D ultrasound images (B-mode) of the quadriceps were obtained from young (26 ± 4 year, n = 8 M, 8 F) and older (70 ± 7 year, n = 7 M, 5 F) adults on two occasions, separated by 6 ± 3 days. With participants in both standing and supine postures, images were collected from five anatomical sites along the anterior (two sites) and lateral (three sites) compartments of the thigh corresponding to 56%, 39%, and 22% (lateral only) of femur length.

Direct and selective pharmacological disruption of the YAP-TEAD interface by IAG933 inhibits Hippo-dependent and RAS-MAPK-altered cancers.

The YAP-TEAD protein-protein interaction mediates YAP oncogenic functions downstream of the Hippo pathway. To date, available YAP-TEAD pharmacologic agents bind into the lipid pocket of TEAD, targeting the interaction indirectly via allosteric changes. However, the consequences of a direct pharmacological disruption of the interface between YAP and TEADs remain largely unexplored.

Membrane Permeability in a Large Macrocyclic Peptide Driven by a Saddle-Shaped Conformation.

The effort to modulate challenging protein targets has stimulated interest in ligands that are larger and more complex than typical small-molecule drugs. While combinatorial techniques such as mRNA display routinely produce high-affinity macrocyclic peptides against classically undruggable targets, poor membrane permeability has limited their use toward primarily extracellular targets. Understanding the passive membrane permeability of macrocyclic peptides would, in principle, improve our ability to design libraries whose leads can be more readily optimized against intracellular targets.

An Appraisal of Pharmacotherapy-Pertinent Literature Published in 2021 and 2022 for Clinicians Caring for Patients With Thermal or Inhalation Injury.

Studies focusing on pharmacotherapy interventions to aid patients after thermal injury are a minor focus in burn injury-centered studies and published across a wide array of journals, which challenges those with limited resources to keep their knowledge current. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Twenty-three geographically dispersed, board-certified pharmacists participated in the review.

Hemostatic Efficacy and Safety of Weight-Based Versus Fixed-Dose 4F-PCC for Vitamin K Antagonist Reversal.

Four-factor prothrombin complex concentrate (4F-PCC) is indicated for vitamin K antagonist (VKA) reversal but is associated with thrombotic events (TE). In 2018, the institution revised 4F-PCC dosing for VKA reversal from INR and weight-based dosing to a fixed-dose of 1500 units. The purpose of this study was to compare hemostatic efficacy and TE rate of fixed-dose 4PCC to weight-based dosing.

Identification of robust yield quantitative trait loci derived from cultivated emmer for durum wheat improvement.

Durum wheat (Triticum turgidum ssp. durum L.) is an important world food crop used to make pasta products.

Sequencing 4.3 million mutations in wheat promoters to understand and modify gene expression.

Wheat is an important contributor to global food security, and further improvements are required to feed a growing human population. Functional genetics and genomics tools can help us to understand the function of different genes and to engineer beneficial changes. In this study, we used a promoter capture assay to sequence 2-kb regions upstream of all high-confidence annotated genes from 1,513 mutagenized plants from the tetraploid wheat variety Kronos.

The Necrotrophic Pathogen Is a Master Manipulator of Wheat Defense.

is a necrotrophic pathogen of wheat that is particularly destructive in major wheat-growing regions of the United States, northern Europe, Australia, and South America. secretes necrotrophic effectors that target wheat susceptibility genes to induce programmed cell death (PCD), resulting in increased colonization of host tissue and, ultimately, sporulation to complete its pathogenic life cycle. Intensive research over the last two decades has led to the functional characterization of five proteinaceous necrotrophic effectors, , , , , and , and three wheat susceptibility genes, , , and Functional characterization has revealed that these effectors, in addition to inducing PCD, have additional roles in pathogenesis, including chitin binding that results in protection from wheat chitinases, blocking defense response signaling, and facilitating plant colonization.

Linkage drag analysis in three Aegilops speltoides introgressions carrying Sr47 in modern durum and hard red spring wheat germplasm.

Yield and quality tests of wheat lines derived from RWG35 show they carry little, or no linkage drag and are the preferred source of Sr47 for stem rust resistance. Three durum wheat (Triticum turgidum L. subsp.

Genome-wide association mapping of resistance to the foliar diseases septoria nodorum blotch and tan spot in a global winter wheat collection.

Unlabelled: Septoria nodorum blotch (SNB) and tan spot, caused by the necrotrophic fungal pathogens and , respectively, often occur together as a leaf spotting disease complex on wheat ( L.). Both pathogens produce necrotrophic effectors (NEs) that contribute to the development of disease.

Association Mapping of Resistance to Tan Spot in the Global Durum Panel.

Tan spot, caused by the necrotrophic fungal pathogen (Ptr), is an important disease of durum and common wheat worldwide. Compared with common wheat, less is known about the genetics and molecular basis of tan spot resistance in durum wheat. We evaluated 510 durum lines from the Global Durum Wheat Panel (GDP) for sensitivity to the necrotrophic effectors (NEs) Ptr ToxA and Ptr ToxB and for reaction to Ptr isolates representing races 1 to 5.

Common framework mutations impact antibody interfacial dynamics and flexibility.

Introduction: With the flood of engineered antibodies, there is a heightened need to elucidate the structural features of antibodies that contribute to specificity, stability, and breadth. While antibody flexibility and interface angle have begun to be explored, design rules have yet to emerge, as their impact on the metrics above remains unclear. Furthermore, the purpose of framework mutations in mature antibodies is highly convoluted.

Prevalence and Importance of the Necrotrophic Effector Gene in Populations Collected from Spring Wheat and Barley.

is a necrotrophic fungal pathogen that causes foliar and root diseases on wheat and barley. These diseases are common in all wheat- and barley-growing regions, with more severe outbreaks occurring under warm and humid conditions. can also infect a wide range of grass species in the family Poaceae and secrete , an important necrotrophic effector also identified other wheat leaf spotting pathogens.

Optimization of highly efficient exogenous-DNA-free Cas9-ribonucleoprotein mediated gene editing in disease susceptibility loci in wheat ().

The advancement of precision engineering for crop trait improvement is important in the face of rapid population growth, climate change, and disease. To this end, targeted double-stranded break technology using RNA-guided Cas9 has been adopted widely for genome editing in plants. or particle bombardment-based delivery of plasmids encoding Cas9 and guide RNA (gRNA) is common, but requires optimization of expression and often results in random integration of plasmid DNA into the plant genome.