Knee Extensor and Flexor Force Control after ACL Injury and Reconstruction: A Systematic Review and Meta-Analysis.

Purpose: Reduced force control after anterior cruciate ligament (ACL) injury and reconstruction may contribute to poor function. Various metrics (linear and nonlinear) have been employed to quantify force control. The aims of this review were to synthesize evidence assessing knee extensor and flexor force control after ACL injury (ACLD) or reconstruction (ACLR) and to investigate the potential effects of injury management (e.

Metagenomics reveals spatial variation in cyanobacterial composition, function, and biosynthetic potential in the Winam Gulf, Lake Victoria, Kenya.

The Winam Gulf in the Kenyan region of Lake Victoria experiences prolific, year-round cyanobacterial harmful algal blooms (cyanoHABs) which pose threats to human, livestock, and ecosystem health. To our knowledge, there is limited molecular research on the gulf's cyanoHABs, and thus, the strategies employed for survival and proliferation by toxigenic cyanobacteria in this region remain largely unexplored. Here, we used metagenomics to analyze the Winam Gulf's cyanobacterial composition, function, and biosynthetic potential.

Engineering a Biosynthetic Pathway for the Production of (+)-Brevianamides A and B in .

The privileged fused-ring system comprising the bicyclo[2.2.2]diazaoctane (BDO) core is prevalent in diketopiperazine (DKP) natural products with potent and diverse biological activities, with some being explored as drug candidates.

Molecular investigation of harmful cyanobacteria reveals hidden risks and niche partitioning in Kenyan Lakes.

Despite the global expansion of cyanobacterial harmful algal blooms (cHABs), research is biased to temperate systems within the global north, such as the Laurentian Great Lakes. This lack of diversity represents a significant gap in the field and jeopardizes the health of those who reside along at-risk watersheds in the global south. The African Great Lake, Lake Victoria, is understudied despite serving as the second largest lake by surface area and demonstrating year-round cHABs.

Optimized production of concanamycins using a rational metabolic engineering strategy.

Plecomacrolides, such as concanamycins and bafilomycins, are potent and specific inhibitors of vacuolar-type ATPase. Concanamycins are 18-membered macrolides with promising therapeutic potential against multiple diseases, including viral infection, osteoporosis, and cancer. Due to the complexity of their total synthesis, the production of concanamycins is only achieved through microbial fermentation.

Ideological diversity of media consumption predicts COVID-19 vaccination.

This study examines the relationship between respondents' vaccine hesitancy, reported media consumption patterns, ideological leanings, and trust in science. A large-scale survey conducted in the US in 2022 (N = 1,646) assessed self-reported COVID-19 vaccination, trust in science, and reported media consumption. Findings show that, regardless of personal ideology, individuals who consumed less conservative media and had a more ideologically diverse media diet were more likely to be fully vaccinated and boosted.

Netupitant Exhibits Potent Activity on Persisters.

In (Mtb), persisters are genotypically drug-sensitive bacteria that nonetheless survive antibiotic treatment. Persisters represent a significant challenge to shortening TB treatment and preventing relapse, underscoring the need for new therapeutic strategies. In this study, we screened 2,336 FDA-approved compounds to identify agents that enhance the sterilizing activity of standard anti-TB drugs and prevent the regrowth of persisters.

Metagenomic sequencing of cyanobacterial-dominated Lake Victoria-an African Great Lake.

We report 40 metagenomic libraries collected from the Winam Gulf of Lake Victoria during May-July of 2022-2023 and an additional eight opportunistic libraries from adjacent Lakes Simbi, Naivasha, and regional river systems. The sampling period captured cyanobacterial bloom events - shedding insight onto community composition and genomic potential.

Synthesis of a Truncated Microcystin Tetrapeptide Molecule from a Partial Mcy Gene Cluster in Microcystis Cultures and Blooms.

spp. threaten freshwater ecosystems through the proliferation of cyanobacterial harmful algal blooms (cyanoHABs) and production of the hepatotoxin, microcystin. While microcystin and its biosynthesis pathway, encoded by the genes, have been well studied for over 50 years, a recent study found that populations in western Lake Erie contain a transcriptionally active partial operon, in which the A2 domain of and are present but the genes are absent.

Predicting bacterial fitness in Mycobacterium tuberculosis with transcriptional regulatory network-informed interpretable machine learning.

(Mtb) is the causative agent of tuberculosis disease, the greatest source of global mortality by a bacterial pathogen. Mtb adapts and responds to diverse stresses such as antibiotics by inducing transcriptional stress-response regulatory programs. Understanding how and when these mycobacterial regulatory programs are activated could enable novel treatment strategies for potentiating the efficacy of new and existing drugs.

Gas-Phase Unfolding Reveals Stability Shifts Associated with Substrate Binding in Modular Polyketide Synthases.

Native mass spectrometry (MS), ion mobility (IM), and collision-induced unfolding (CIU) have all been widely used to study the binding of small molecules to proteins and their complexes. Despite many successes in detecting subtle gas-phase stability differences in smaller systems dominated by single-domain subunits, studies targeting complexes comprised of large, multidomain subunits still face many challenges. For example, polyketide synthases (PKSs) are multiprotein enzymes that use their modular architecture to produce polyketide natural products and form the basis for nearly one-third of pharmaceuticals.

Time-Resolved Ion Mobility-Mass Spectrometry Reveals Structural Transitions in the Disassembly of Modular Polyketide Syntheses.

The type 1 polyketide synthase (PKS) assembly line uses its modular structure to produce polyketide natural products that form the basis of many pharmaceuticals. Currently, several cryoelectron microscopy (cryo-EM) structures of a multidomain PKS module have been constructed, but much remains to be learned. Here we utilize ion-mobility mass spectrometry (IM-MS) to record size and shape information and detect different conformational states of a 207 kDa didomain dimer comprised of ketosynthase (KS) and acyl transferase (AT), excised from full-length module.

Test-Retest Reliability and Visual Perturbation Performance Costs During 2 Reactive Agility Tasks.

Context: High secondary injury rates after orthopedic surgeries have motivated concern toward the construct validity of return-to-sport test batteries, as it is evident that common strength and functional assessments fail to elicit pertinent behaviors like visual search and reactive decision making. This study aimed to establish the test-retest reliability of 2 reactive agility tasks and evaluate the impact of visual perturbation on physical performance.

Methods: Fourteen physically active individuals completed 2 agility tasks with reaction time (ie, 4 corner agility), working memory, and pathfinding (ie, color recall) components.

Discovery of Uncommon Tryptophan-Containing Diketopiperazines from CBS 101889 Using an Heterologous Expression System.

Fungal secondary metabolite (SM) biosynthetic gene clusters (BGCs) containing dimethylallyltryptophan synthases (DMATSs) produce structurally diverse prenylated indole alkaloids with wide-ranging activities that have vast potential as human therapeutics. To discover new natural products produced by DMATSs, we mined the Department of Energy Joint Genome Institute's MycoCosm database for DMATS-containing BGCs. We found a DMATS BGC in CBS 101889, which also contains a nonribosomal peptide synthetase (NRPS).

Substrate Trapping in Polyketide Synthase Thioesterase Domains: Structural Basis for Macrolactone Formation.

Emerging antibiotic resistance requires continual improvement in the arsenal of antimicrobial drugs, especially the critical macrolide antibiotics. Formation of the macrolactone scaffold of these polyketide natural products is catalyzed by a modular polyketide synthase (PKS) thioesterase (TE). The TE accepts a linear polyketide substrate from the termina PKS acyl carrier protein to generate an acyl-enzyme adduct that is resolved by attack of a substrate hydroxyl group to form the macrolactone.

Discovering type I cis-AT polyketides through computational mass spectrometry and genome mining with Seq2PKS.

Type 1 polyketides are a major class of natural products used as antiviral, antibiotic, antifungal, antiparasitic, immunosuppressive, and antitumor drugs. Analysis of public microbial genomes leads to the discovery of over sixty thousand type 1 polyketide gene clusters. However, the molecular products of only about a hundred of these clusters are characterized, leaving most metabolites unknown.

Metabologenomics reveals strain-level genetic and chemical diversity of secondary metabolism.

spp. are renowned for producing the hepatotoxin microcystin in freshwater cyanobacterial harmful algal blooms around the world, threatening drinking water supplies and public and environmental health. However, genomes also harbor numerous biosynthetic gene clusters (BGCs) encoding the biosynthesis of other secondary metabolites, including many with toxic properties.

-to- Acyl Transfer as an Enabling Strategy in Asymmetric and Chemoenzymatic Synthesis.

The observation of thioester-mediated acyl transfer processes in nature has inspired the development of novel protein synthesis and functionalization methodologies. The chemoselective transfer of an acyl group from -to- is the basis of several powerful ligation strategies. In this work, we sought to apply the reverse process, the transfer of an acyl group from -to-, as a method to convert stable chiral amides into more reactive thioesters.