HSP90 buffers deleterious genetic variations in .

Protein-folding chaperone HSP90 buffers genetic variation in diverse organisms, but the clinical significance of HSP90 buffering in disease remains unclear. Here, we show that HSP90 buffers mutations in the BRCT domain of BRCA1. HSP90-buffered mutations encode protein variants that retain interactions with partner proteins and rely on HSP90 for protein stability and function in cell survival.

Nile Red Fluorescence: Where's the Twist?

Nile Red is a fluorescent dye used extensively in bioimaging due to its strong solvatochromism. The photophysics underpinning Nile Red's fluorescence has been disputed for decades, with some studies claiming that the dye fluoresces from two excited states and/or that the main emissive state is twisted and intramolecular charge-transfer (ICT) in character as opposed to planar ICT (PICT). To resolve these long-standing questions, a combined experimental and theoretical study was used to unravel the mechanism of Nile Red's fluorescence.

Selection for robust metabolism in domesticated yeasts is driven by adaptation to Hsp90 stress.

Protein folding both promotes and constrains adaptive evolution. We uncover this surprising duality in the role of the protein-folding chaperone heat shock protein 90 (Hsp90) in maintaining the integrity of yeast metabolism amid proteotoxic stressors within industrial domestication niches. Ethanol disrupts critical Hsp90-dependent metabolic pathways and exerts strong selective pressure for redundant duplications of key genes within these pathways, yielding the classical genomic signatures of beer and bread domestication.

Slow vibrational relaxation drives ultrafast formation of photoexcited polaron pair states in glycolated conjugated polymers.

Glycol sidechains are often used to enhance the performance of organic photoconversion and electrochemical devices. Herein, we study their effects on electronic states and electronic properties. We find that polymer glycolation not only induces more disordered packing, but also results in a higher reorganisation energy due to more localised π-electron density.

Femtosecond to Microsecond Observation of Photochemical Pathways in Nitroaromatic Phototriggers Using Transient Absorption Spectroscopy.

The synthetic accessibility and tolerance to structural modification of phototriggered compounds (PTs) based on the - nitrobenzene (ONB) protecting group have encouraged a myriad of applications including optimization of biological activity, and supramolecular polymerization. Here, a combination of ultrafast transient absorption spectroscopy techniques is used to study the multistep photochemistry of two nitroaromatic phototriggers based on the ONB chromophore, -(4,5-dimethoxy-2-nitrobenzyl)-l-serine (DMNB-Ser) and [(2-nitrophenyl)methyl]-l-tyrosine hydrochloride (NB-Tyr), in DMSO solutions on femtosecond to microsecond time scales following the absorption of UV light. From a common -S excited state, the PTs can either undergo excited state intramolecular hydrogen transfer (ESIHT) to an -S isomer within the singlet state manifold, leading to direct S → S internal conversion through a conical intersection, or competitive intersystem crossing (ISC) to access the triplet state manifold on time scales of (1.

Unraveling the Ultrafast Photochemical Dynamics of Nitrobenzene in Aqueous Solution.

Nitroaromatic compounds are major constituents of the brown carbon aerosol particles in the troposphere that absorb near-ultraviolet (UV) and visible solar radiation and have a profound effect on the Earth's climate. The primary sources of brown carbon include biomass burning, forest fires, and residential burning of biofuels, and an important secondary source is photochemistry in aqueous cloud and fog droplets. Nitrobenzene is the smallest nitroaromatic molecule and a model for the photochemical behavior of larger nitroaromatic compounds.

Structural dynamics around a hydrogen bond: Investigating the effect of hydrogen bond strengths on the excited state dynamics of carboxylic acid dimers.

The photochemical dynamics of the acetic acid and trifluoro-acetic acid dimers in hexane are studied using time-resolved infrared absorption spectroscopy and ab initio electronic structure calculations. The different hydrogen bond strengths of the two systems lead to changes in the character of the accessed excited states and in the timescales of the initial structural rearrangement that define the early time dynamics following UV excitation. The much stronger hydrogen bonding in the acetic acid dimer stabilizes the system against dissociation.

A Novel Framework for Image Matching and Stitching for Moving Car Inspection under Illumination Challenges.

Vehicle exterior inspection is a critical operation for identifying defects and ensuring the overall safety and integrity of vehicles. Visual-based inspection of moving objects, such as vehicles within dynamic environments abounding with reflections, presents significant challenges, especially when time and accuracy are of paramount importance. Conventional exterior inspections of vehicles require substantial labor, which is both costly and prone to errors.

Protein-folding chaperones predict structure-function relationships and cancer risk in BRCA1 mutation carriers.

Predicting the risk of cancer mutations is critical for early detection and prevention, but differences in allelic severity of human carriers confound risk predictions. Here, we elucidate protein folding as a cellular mechanism driving differences in mutation severity of tumor suppressor BRCA1. Using a high-throughput protein-protein interaction assay, we show that protein-folding chaperone binding patterns predict the pathogenicity of variants in the BRCA1 C-terminal (BRCT) domain.

A versatile high-average-power ultrafast infrared driver tailored for high-harmonic generation and vibrational spectroscopy.

We report on an ultrafast infrared optical parametric chirped-pulse amplifier (OPCPA), pumped by a 200-W thin-disk Yb-based regenerative amplifier at a repetition rate of 100 kHz. The OPCPA is tunable in the spectral range 1.4-3.

Ethanol Drives Evolution of Hsp90-Dependent Robustness by Redundancy in Yeast Domestication.

Protein folding promotes and constrains adaptive evolution. We uncover this surprising duality in the role the protein-folding chaperone Hsp90 plays in mediating the interplay between proteome and the genome which acts to maintain the integrity of yeast metabolism in the face of proteotoxic stressors in anthropic niches. Of great industrial relevance, ethanol concentrations generated by fermentation in the making of beer and bread disrupt critical Hsp90-dependent nodes of metabolism and exert strong selective pressure for increased copy number of key genes encoding components of these nodes, yielding the classical genetic signatures of beer and bread domestication.

Protein-Folding Chaperones Predict Structure-Function Relationships and Cancer Risk in Mutation Carriers.

Unlabelled: Identifying pathogenic mutations and predicting their impact on protein structure, function and phenotype remain major challenges in genome sciences. Protein-folding chaperones participate in structure-function relationships by facilitating the folding of protein variants encoded by mutant genes. Here, we utilize a high-throughput protein-protein interaction assay to test HSP70 and HSP90 chaperone interactions as predictors of pathogenicity for variants in the tumor suppressor BRCA1.

Ultrafast electronic, infrared, and X-ray absorption spectroscopy study of Cu(I) phosphine diimine complexes.

The study aims to understand the role of the transient bonding in the interplay between the structural and electronic changes in heteroleptic Cu(I) diimine diphosphine complexes. This is an emerging class of photosensitisers which absorb in the red region of the spectrum, whilst retaining a sufficiently long excited state lifetime. Here, the dynamics of these complexes are explored by transient absorption (TA) and time-resolved infrared (TRIR) spectroscopy, which reveal ultrafast intersystem crossing and structural distortion occurring.

Epichaperome inhibition targets TP53-mutant AML and AML stem/progenitor cells.

TP 53-mutant acute myeloid leukemia (AML) remains the ultimate therapeutic challenge. Epichaperomes, formed in malignant cells, consist of heat shock protein 90 (HSP90) and associated proteins that support the maturation, activity, and stability of oncogenic kinases and transcription factors including mutant p53. High-throughput drug screening identified HSP90 inhibitors as top hits in isogenic TP53-wild-type (WT) and -mutant AML cells.

An ELISA-based platform for rapid identification of structure-dependent nucleic acid-protein interactions detects novel DNA triplex interactors.

Unusual nucleic acid structures play vital roles as intermediates in many cellular processes and, in the case of peptide nucleic acid (PNA)-mediated triplexes, are leveraged as tools for therapeutic gene editing. However, due to their transient nature, an understanding of the factors that interact with and process dynamic nucleic acid structures remains limited. Here, we developed snapELISA (structure-specific nucleic acid-binding protein ELISA), a rapid high-throughput platform to interrogate and compare up to 2688 parallel nucleic acid structure-protein interactions in vitro.

Indoor Visual Exploration with Multi-Rotor Aerial Robotic Vehicles.

In this work, we develop a reactive algorithm for autonomous exploration of indoor, unknown environments for multiple autonomous multi-rotor robots. The novelty of our approach rests on a two-level control architecture comprised of an Artificial-Harmonic Potential Field (AHPF) for navigation and a low-level tracking controller. Owing to the AHPF properties, the field is provably safe while guaranteeing workspace exploration.

Circadian effects on neural blockade of levobupivacaine and fentanyl intrathecal administration for caesarian section.

Circadian variations in biological rhythms affect the pharmacological properties of many anaesthetic agents, suggesting circadian patterns of local anaesthetics' activity in labour pain analgesia, with important differences among diurnal and nocturnal phases.

Laparoscopic cholecystectomy under total intravenous anaesthesia in a patient with myotonic dystrophy type 1 (Steinert's disease) - a case report.

Myotonic dystrophy type 1 or Steinert's disease is an autosomal dominant multisystem disease which is characterized by consistent contracture of muscle following stimulation (myotonia). Hypothermia, shivering, mechanical or electric stimulation during surgery can precipitate episodes of myotonia which may complicate the course of anaesthesia. The present case report focuses on successful strategies for providing general anaesthesia for laparoscopic cholecystectomy in a patient affected by this genetic disorder, at a hospital which does not have the facility for postoperative ventilation.

Ultrafast Triggering of Insulator-Metal Transition in Two-Dimensional VSe.

The transition-metal dichalcogenide VSe exhibits an increased charge density wave transition temperature and an emerging insulating phase when thinned to a single layer. Here, we investigate the interplay of electronic and lattice degrees of freedom that underpin these phases in single-layer VSe using ultrafast pump-probe photoemission spectroscopy. In the insulating state, we observe a light-induced closure of the energy gap, which we disentangle from the ensuing hot carrier dynamics by fitting a model spectral function to the time-dependent photoemission intensity.

Photodissociation dynamics of methyl iodide probed using femtosecond extreme ultraviolet photoelectron spectroscopy.

Femtosecond pump-probe photoelectron spectroscopy measurements using an extreme ultraviolet probe have been made on the photodissociation dynamics of UV (269 nm) excited CH3I. The UV excitation leads to population of the 3Q0 state which rapidly dissociates. The dissociation is manifested as shifts in the measured photoelectron kinetic energy that map the extending C-I bond.

Three-dimensional covariance-map imaging of molecular structure and dynamics on the ultrafast timescale.

Ultrafast laser pump-probe methods allow chemical reactions to be followed in real time, and have provided unprecedented insight into fundamental aspects of chemical reactivity. While evolution of the electronic structure of the system under study is evident from changes in the observed spectral signatures, information on rearrangement of the nuclear framework is generally obtained indirectly. Disentangling contributions to the signal arising from competing photochemical pathways can also be challenging.

Robust Formation Control for Multiple Underwater Vehicles.

This paper addresses the distance-based formation control problem for multiple Autonomous Underwater Vehicles (AUVs) in a leader-follower architecture. The leading AUV is assigned a task to track a desired trajectory and the following AUVs try to set up a predefined formation structure by attaining specific distances among their neighboring AUVs, while avoiding collisions and enabling at the same time relative localization. More specifically, a decentralized control protocol of minimal complexity is proposed that achieves prescribed, arbitrarily fast and accurate formation establishment.

Photodissociation dynamics of CHI probed via multiphoton ionisation photoelectron spectroscopy.

The dissociation dynamics of CHI is investigated on the red (269 nm) and blue (255 nm) side of the absorption maximum of the A-band. Using a multiphoton ionisation probe in a time-resolved photoelectron imaging experiment we observe very different dynamics at the two wavelengths, with significant differences in the measured lifetime and dynamic structure. The differences are explained in terms of changes in excitation cross-sections of the accessible Q and Q states and the subsequent dynamics upon each of them.

On-the-Fly Femtosecond Action Spectroscopy of Charged Cyanine Dyes: Electronic Structure versus Geometry.

Understanding optical properties of molecular dyes is required to drive progress in molecular photonics. This requires a fundamental comprehension of the role of electronic structure, geometry, and interactions with the environment in order to guide molecular engineering strategies. In this context, we studied charged cyanine dye molecules in the gas phase with a controlled microenvironment to unravel the origin of the spectral tuning of this class of molecules.

A generalized vibronic-coupling Hamiltonian for molecules without symmetry: Application to the photoisomerization of benzopyran.

We present a model for the lowest two potential energy surfaces (PESs) that describe the photoinduced ring-opening reaction of benzopyran taken as a model compound to study the photochromic ring-opening reaction of indolinobenzospiropyran and its evolution toward its open-chain analog. The PESs are expressed in terms of three effective rectilinear coordinates. One corresponds to the direction between the equilibrium geometry in the electronic ground state, referred to as the Franck-Condon geometry, and the minimum of conical intersection (CI), while the other two span the two-dimensional branching space at the CI.