Genome graphs reveal the importance of structural variation in evolution and drug resistance.

Structural variants (SVs) are increasingly recognized as key drivers of bacterial evolution, yet their role has not been explored thoroughly. This is due to limitations in traditional short-read sequencing and linear reference-based analyses, which can miss complex structural changes. Tuberculosis (TB), a disease caused by (), remains a major global health concern.

TBpore cluster: A novel phylogenetic pipeline for tuberculosis transmission studies using nanopore next-generation sequencing data.

Background: Molecular typing of Mycobacterium tuberculosis complex isolates enhances understanding of tuberculosis (TB) transmission dynamics, supporting public health efforts in outbreak investigations. This study aims to validate TBpore, a novel bioinformatic pipeline for clustering TB transmission isolates using Oxford Nanopore Technology (ONT) data and comparing it against conventional Mycobacterial Interspersed Repetitive-Unit Variable Number (MIRU-VNTR) typing and Illumina sequencing.

Methodology/principal Findings: This retrospective case-control study included 58 clinical isolates from two TB outbreaks in Canada, previously characterized by public health investigations and MIRU-VNTR typing.

How Geometric Constraints Control the Hydride Position and Activity in [NiFe]-Hydrogenases and Their Biomimetic Complexes.

The active site in [NiFe]-hydrogenase features a bridging hydride between the Ni and Fe, displaced toward the Ni. However, all synthetic models reported to date exhibit a hydride displaced toward Fe and display low turnover frequencies for H evolution. Understanding the factors governing the hydride position and activity of and biomimetic complexes is crucial for developing efficient hydrogen-evolving catalysts.

Origin of Intramolecular versus Intermolecular C-H Arene Activation Selectivity by Cyclopentadienyl-Triphenylphosphine Iridium.

Photolysis of (η-CMe)Ir(PPh)(H) in benzene generates the 16-electron (16e) complex (η-CMe)Ir(PPh) that undergoes competitive molecular ortho-metalation with a phenyl group from -PPh and molecular C-H activation with benzene. Previous density functional theory (DFT) studies identified the molecular π-complex and the molecular benzene π-complex intermediates and their corresponding C-H activation transition states. However, neither the mechanism of interconversion between these intermediates nor the origin of molecular versus molecular pathway selectivity has been established.

A sulfur-templated Ni-Ni' coordination polymer that relies on a polarizable nickel nitrosyl hub.

The templating properties of a diaza-nickel--dithiolate towards triphenylphosphine gold(I), yielding a [Ni(NS)·2Au(PPh)] complex (T. A. Pinder, S.

A Caged Neutral 17-Valence-Electron Iron(I) Radical [Fe(CO)(Cl)(P((CH))P)]: Synthetic, Structural, Spectroscopic, Redox, and Computational Studies.

UV irradiation of yellow CHCl solutions of -Fe(CO)(P((CH))P) () and PMe (10 equiv) gives, in addition to the previously reported dibridgehead diphosphine P((CH))P (46%), a green paramagnetic complex that crystallography shows to be the trigonal-bipyramidal iron(I) radical -[Fe(CO)(Cl)(P((CH))P)] (; 31% after workup). This is a rare example of an isolable species of the formula [Fe(CO)(L)(X)] ( = 0-3, L = two-electron-donor ligand; X = one-electron-donor ligand). Analogous precursors with longer P(CH)P segments ( = 12, 14, 16, 18) give only the demetalated diphosphines, and a rationale is proposed.

Site specific redox properties in ligand differentiated di-nickel complexes inspired by the acetyl CoA synthase active site.

Bimetallic transition metal complexes with site-specific redox properties offer a versatile platform for understanding electron polarization, intramolecular electron transfer processes, and customizing electronic and magnetic properties that might impact reactivity and catalyst design. Inspired by the dissymmetric nickel sites in the Acetyl CoA Synthase (ACS) Active Site, three new bimetallic Ni(NS)-Ni(SCR) complexes based on Ni(NS) metalloligand donor synthons, Ni, in mimicry of the nickel site distal to the redox-active iron sulfur cluster of ACS, and nickel dithiolene receiver units, designated as Ni, the nickel proximal to the 4Fe4S cluster, were combined to explore the influence of ligand environment on electronic structure and redox properties of each unit. The combination of synthons gave a matrix of three S-bridged dinickel complexes, characterized by X-ray crystallography, and appropriate spectroscopies.

Pangenome databases improve host removal and mycobacteria classification from clinical metagenomic data.

Background: Culture-free real-time sequencing of clinical metagenomic samples promises both rapid pathogen detection and antimicrobial resistance profiling. However, this approach introduces the risk of patient DNA leakage. To mitigate this risk, we need near-comprehensive removal of human DNA sequences at the point of sequencing, typically involving the use of resource-constrained devices.

Concordance of targeted and whole genome sequencing for Mycobacterium tuberculosis genotypic drug susceptibility testing.

Targeted Next Generation Sequencing (tNGS) and Whole Genome Sequencing (WGS) are increasingly used for genotypic drug susceptibility testing (gDST) of Mycobacterium tuberculosis. Thirty-two multi-drugs resistant and 40 drug susceptible isolates from Madagascar were tested with Deeplex® Myc-TB and WGS using the Mykrobe analysis pipeline. Sixty-four of 72 (89 %) yielded concordant categorical gDST results for drugs tested by both assays.

Theoretical Investigation of Linear Relationships between the Dihedral Torsion Angles and Diosmium Bond Distances in Diosmium Sawhorse Complexes.

Strong linear relationships between their C-Os-Os-C dihedral angles and their Os-Os bond distances in diosmium sawhorse complexes Os(u-OCR)(CO)L (L = CO and/or PR) form two trendlines depending upon the presence or absence of terminal phosphines. These trends appear unrelated to the basicity of the bridging ligand or the number of phosphines. The mathematical derivation of the relationship between the O-Os-Os-O dihedral angle and the Os-Os bond distance shows how the other geometric parameters affect this relationship.

Sulfur Lone Pairs Control Topology in Heterotrimetallic Complexes: An Experimental and Theoretical Study.

Heterotrimetallic complexes with (NS)M metallodithiolates, M = Ni, [Fe(NO)], and [Co(NO)], as bidentate chelating ligands to a central trans-Cr(NO)(MeCN) unit were characterized as the first members of a new class, , , . The complexes exhibit a cisoid structural topology, ascribed to the stereoactivity of the available lone pair(s) on the sulfur donors, resulting in a dispersed, electropositive pocket from the N/N and N/S hydrocarbon linkers wherein the Cr-NO site is housed. Computational studies explored alternative isomers (transoid and inverted cisoid) that suggest a combination of electronic and steric effects govern the geometrical selectivity.

Magnetic coupling between Fe(NO) spin probe ligands through diamagnetic Ni, Pd and Pt tetrathiolate bridges.

Reaction of the nitrosylated-iron metallodithiolate ligand, paramagnetic (NO)Fe(NS), with [M(CHCN)][BF] salts (M = Ni, Pd, and Pt; = 4 or 6) affords di-radical tri-metallic complexes in a stairstep type arrangement ([FeMFe], M = Ni, Pd, and Pt), with the central group 10 metal held in a MS square plane. These isostructural compounds have nearly identical (NO) stretching values, isomer shifts, and electrochemical properties, but vary in their magnetic properties. Despite the intramolecular Fe⋯Fe distances of 6 Å, antiferromagnetic coupling is observed between {Fe(NO)} units as established by magnetic susceptibility, EPR, and DFT studies.

Drug resistance prediction for with reference graphs.

Tuberculosis is a global pandemic disease with a rising burden of antimicrobial resistance. As a result, the World Health Organization (WHO) has a goal of enabling universal access to drug susceptibility testing (DST). Given the slowness of and infrastructure requirements for phenotypic DST, whole-genome sequencing, followed by genotype-based prediction of DST, now provides a route to achieving this.

Dimetalloylene (M-E-M) Complexes of Heavier Main Group Elements Ge, Sn, Pb, Bi via Cleavage of E-X Bonds (X=N(SiMe ) , OtBu) with an Iridium Hydride.

Reactions of the Ir hydride [ BDI ]IrH {BDI=(Dipp)NC(Me)CH(Me)CN(Dipp); Dipp=2,6-iPr C H } with E[N(SiMe ) ] (E=Sn, Pb) afforded the unusual dimeric dimetallotetrylenes ([ BDI ]IrH) (μ -E) in good yields. Moreover, ([ BDI ]IrH) (μ -Ge) was formed in situ from thermal decomposition of [ BDI ]Ir(H) Ge[N(SiMe ) ] . These reactions are accompanied by liberation of HN(SiMe ) and H through the apparent cleavage of an E-N(SiMe ) bond by Ir-H.

A Prospective Open-Label Study for Treatment of Infraorbital Hollows Using a Volumizing Hyaluronic Acid Filler.

This study aimed to prospectively evaluate the effectiveness, patient satisfaction, and early adverse events of using the hyaluronic acid filler VYC-20L for the treatment of infraorbital hollowing. A total of 21 participants underwent injection of VYC-20L. FACE-Q satisfaction surveys before and after treatment along with early adverse events surveys were conducted.

Improving a Methane C-H Activation Complex by Metal and Ligand Alterations from Computational Results.

We present results for a series of complexes derived from a titanium complex capable of activating C-H bonds under mild conditions (PNP)Ti═CHBu(CHBu), where PNP = N[2-PPr-4-methylphenyl]. In addition to the initial activation of methane, a tautomerization reaction to a terminal methylidene is also explored due to methylidene's potential use as a synthetic starting point. Analogous complexes with other low-cost 3d transition metals were studied, such as scandium, titanium, vanadium, and chromium as both isoelectronic and isocharged complexes.

Genomic Sequencing from Sputum for Tuberculosis Disease Diagnosis, Lineage Determination, and Drug Susceptibility Prediction.

Universal access to drug susceptibility testing for newly diagnosed tuberculosis patients is recommended. Access to culture-based diagnostics remains limited, and targeted molecular assays are vulnerable to emerging resistance mutations. Improved protocols for direct-from-sputum Mycobacterium tuberculosis sequencing would accelerate access to comprehensive drug susceptibility testing and molecular typing.

Evaluation of Nanopore sequencing for Mycobacterium tuberculosis drug susceptibility testing and outbreak investigation: a genomic analysis.

Background: Mycobacterium tuberculosis whole-genome sequencing (WGS) has been widely used for genotypic drug susceptibility testing (DST) and outbreak investigation. For both applications, Illumina technology is used by most public health laboratories; however, Nanopore technology developed by Oxford Nanopore Technologies has not been thoroughly evaluated. The aim of this study was to determine whether Nanopore sequencing data can provide equivalent information to Illumina for transmission clustering and genotypic DST for M tuberculosis.

Mechanism of Coupling of Methylidene to Ethylene Ligands in Dimetallic Assemblies; Computational Investigation of a Model for a Key Step in Catalytic C Chemistry.

Methylidene complexes often couple to ethylene complexes, but the mechanistic insight is scant. The path by which two cations [(η-CH)Re(NO)(PPh)(═CH)] () transform (CHCl/acetonitrile) to [(η-CH)Re(NO)(PPh)(HC═CH)] () and [(η-CH)Re(NO)(PPh)(NCCH)] is studied by density functional theory. Experiments provide a number of constraints such as the second-order rate in ; no prior ligand dissociation/exchange; a faster reaction of ()- with ()- than with ()- ("enantiomer self-recognition").

Water: new aspect of hydrogen bonding in the solid state.

All water-water contacts in the crystal structures from the Cambridge Structural Database with ≤ 4.0 Å have been found. These contacts were analysed on the basis of their geometries and interaction energies from CCSD(T)/CBS calculations.

Complexation of Astatine(III) with Ketones: Roles of NO Counterion and Exploration of Possible Binding Modes.

Ketones have been proven effective in extracting astatine(III) from aqueous solvents. Previous theoretical studies suggested a mechanism where the "sp" lone pair on the carbonyl oxygen donates electron density into the π system of the AtO molecular cation to form a dative-type bond. In this study, co-extraction of NO as AtO(NO)·(O═CRR) species into the organic phase appears to be a key factor.

Minos: variant adjudication and joint genotyping of cohorts of bacterial genomes.

There are many short-read variant-calling tools, with different strengths and weaknesses. We present a tool, Minos, which combines outputs from arbitrary variant callers, increasing recall without loss of precision. We benchmark on 62 samples from three bacterial species and an outbreak of 385 Mycobacterium tuberculosis samples.

Cooperative redox and spin activity from three redox congeners of sulfur-bridged iron nitrosyl and nickel dithiolene complexes.

The synthesis of sulfur-bridged Fe-Ni heterobimetallics was inspired by Nature's strategies to "trick" abundant first row transition metals into enabling 2-electron processes: redox-active ligands (including pendant iron-sulfur clusters) and proximal metals. Our design to have redox-active ligands on each metal, NO on iron and dithiolene on nickel, resulted in the observation of unexpectedly intricate physical properties. The metallodithiolate, (NO)Fe(NS), reacts with a labile ligand derivative of [Ni(SCPh)], Ni, yielding the expected S-bridged neutral adduct, , containing a doublet {Fe(NO)}.