Phase 1 study of the safety, tolerability, and pharmacokinetics of a synthetic macrocyclic peptide antibiotic (BRII-693) in healthy adult participants.

BRII-693 is a next-generation intravenous (IV)-administered synthetic macrocyclic peptide antibiotic for infections caused by drug-resistant gram-negative pathogens. This single-center, randomized, double-blind, placebo-controlled phase 1 study investigated the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of BRII-693 in 104 healthy participants. In single-dose cohorts, 10-400 mg of BRII-693 was evaluated in eight participants (six active; two placebo) per cohort.

The strand exchange domain of tumor suppressor PALB2 is intrinsically disordered and promotes oligomerization-dependent DNA compaction.

The partner and localizer of BRCA2 (PALB2) is a scaffold protein linking BRCA1 with BRCA2 and RAD51 during homologous recombination (HR). PALB2 interaction with DNA strongly enhances HR in cells, while the PALB2 DNA-binding domain (PALB2-DBD) supports DNA strand exchange . We determined that PALB2-DBD is intrinsically disordered beyond a single N-terminal α-helix.

χ-Conotoxins are an Evolutionary Innovation of Mollusk-Hunting Cone Snails as a Counter-Adaptation to Prey Defense.

Mollusk-hunting (molluscivorous) cone snails belong to a monophyletic group in Conus, a genus of venomous marine snails. The molluscivorous lineage evolved from ancestral worm-hunting (vermivorous) snails ∼18 Ma. To enable the shift to a molluscivorous lifestyle, molluscivorous cone snails must solve biological problems encountered when hunting other gastropods, namely: (i) preventing prey escape and (ii) overcoming the formidable defense of the prey in the form of the molluscan shell, a problem unique to molluscivorous Conus.

Comparison of outcomes in dogs undergoing hiatal hernia repair with and without use of a gastropexy: 41 cases (2012-2022).

Objectives: To determine the difference in complication rate, gastrointestinal grade and requirement for ongoing medical and/or surgical management following hiatal hernia repair in dogs with and without gastropexy.

Materials And Methods: Clinical records were reviewed retrospectively for dogs that had undergone surgical hiatal hernia repair at two veterinary referral centres between April 2012 and March 2022. Pre-operative grading of gastrointestinal signs and brachycephalic obstructive airway syndrome was performed.

Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study.

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT).