Psychiatric diagnoses are common after liver transplantation and are associated with increased health care utilization and patient financial burden.

Psychiatric disorders after liver transplantation (LT) are associated with worse patient and graft outcomes, which may be amplified by inadequate treatment. We aimed to characterize the burden of psychiatric disorders, treatment patterns, and associated financial burden among liver transplantation recipients (LTRs). IQVIA PharMetrics (R) Plus for Academics-a large health plan claims database representative of the commercially insured US population-was used to identify psychiatric diagnoses among adult LTRs and assess treatment.

The financial burden after liver transplantation is significant among commercially insured adults: A large US National Cohort.

Liver transplantation (LT) is lifesaving for patients with cirrhosis; however, the resultant financial burden to patients has not been well characterized. We aimed to provide a nationally representative portrayal of patient financial burden after LT. Adult recipients of LT from 2006 to 2021 were identified using IQVIA PharMetrics® Plus for Academics-a large nationally representative claims database of commercially insured Americans.

Tuning of B photochemistry in the CarH photoreceptor to avoid radical photoproducts.

Time-resolved infrared spectroscopy reveals the flow of electron density through coenzyme B in the light-activated, bacterial transcriptional regulator, CarH. The protein stabilises a series of charge transfer states that result in a photoresponse that avoids reactive, and potentially damaging, radical photoproducts.

Highlighter: An optogenetic system for high-resolution gene expression control in plants.

Optogenetic actuators have revolutionized the resolution at which biological processes can be controlled. In plants, deployment of optogenetics is challenging due to the need for these light-responsive systems to function in the context of horticultural light environments. Furthermore, many available optogenetic actuators are based on plant photoreceptors that might crosstalk with endogenous signaling processes, while others depend on exogenously supplied cofactors.

Essential elements of radical pair magnetosensitivity in Drosophila.

Many animals use Earth's magnetic field (also known as the geomagnetic field) for navigation. The favoured mechanism for magnetosensitivity involves a blue-light-activated electron-transfer reaction between flavin adenine dinucleotide (FAD) and a chain of tryptophan residues within the photoreceptor protein CRYPTOCHROME (CRY). The spin-state of the resultant radical pair, and therefore the concentration of CRY in its active state, is influenced by the geomagnetic field.

Investigating radical pair reaction dynamics of B coenzymes 2: Time-resolved electron paramagnetic resonance spectroscopy.

The chemistry of B coenzymes is highly sensitive to the nature of their upper axial ligand and can be further tuned by their environment. Methylcobalamin, for example, generates RPs photochemically but undergoes non-radical biochemistry when bound to its dependent enzymes. Owing to the transient nature of the reaction intermediates, it remains a challenge to investigate how their environment controls reactivity.

Investigating radical pair reaction dynamics of B coenzymes 1: Transient absorption spectroscopy and magnetic field effects.

B coenzymes are vital to healthy biological function across nature. They undergo radical chemistry in a variety of contexts, where spin-correlated radical pairs can be generated both thermally and photochemically. Owing to the unusual magnetic properties of B radical pairs, however, most of the reaction and spin dynamics occur on a timescale (picoseconds-nanoseconds) that cannot be resolved by most measurement techniques.

Interplay between chromophore binding and domain assembly by the B-dependent photoreceptor protein, CarH.

Organisms across the natural world respond to their environment through the action of photoreceptor proteins. The vitamin B-dependent photoreceptor, CarH, is a bacterial transcriptional regulator that controls the biosynthesis of carotenoids to protect against photo-oxidative stress. The binding of B to CarH monomers in the dark results in the formation of a homo-tetramer that complexes with DNA; B photochemistry results in tetramer dissociation, releasing DNA for transcription.

Histologic evaluation of therapeutic responses in ischemic myocardium elicited by dual growth factor delivery from composite glycosaminoglycan hydrogels.

In this project, the ability of dual growth factor-preloaded, silk-reinforced, composite hyaluronic acid-based hydrogels to elicit advantageous histologic responses when secured to ischemic myocardium was evaluated in vivo. Reinforced hydrogels containing both Vascular Endothelial Growth Factor (VEGF) and Platelet-derived Growth Factor (PDGF) were prepared by crosslinking chemically modified hyaluronic acid and heparin with poly(ethylene glycol)-diacrylate around a reinforcing silk mesh. Composite patches were sutured to the ventricular surface of ischemic myocardium in Sprague-Dawley rats, and the resulting angiogenic response was followed for 28 days.

Assessing the Covalent Attachment and Energy Transfer Capabilities of Upconverting Phosphors With Cofactor Containing Bioactive Enzymes.

Upconverting phosphors (UCPs) convert multiple low energy photons into higher energy emission via the process of photon upconversion and offer an attractive alternative to organic fluorophores for use as luminescent probes. Examples of biosensors utilizing the apparent energy transfer of UCPs and nanophosphors (UCNPs) with biomolecules have started to appear in the literature but very few exploit the covalent anchoring of the biomolecule to the surface of the UCP to improve the sensitivity of the systems. Here, we demonstrate a robust and versatile method for the covalent attachment of biomolecules to the surface of a variety of UCPs and UCNPs in which the UCPs were capped with functionalized silica in order to provide a surface to covalently conjugate biomolecules with surface-accessible cysteines.

Evaluating spectral overlap with the degree of quenching in UCP luminescence energy transfer systems.

The use of organic based fluorophores has been firmly established as a key tool in the biological sciences, with many biological-sensing methods taking advantage of Förster Resonance Energy Transfer (FRET) between different fluorescent organic based dyes following one photon excitation. Nevertheless, the employment of UV-visible absorbing dyes as fluorescent tags and markers typically suffer from several drawbacks including relatively high energy of excitation wavelength, photobleaching and competitive autofluorescence, which often limits their effectiveness and longevity bothand. As an alternative, lanthanide doped upconverting phosphors (UCP) have emerged as a new class of materials for use in optical imaging and RET sensing; they exhibit high photo- and chemical stability and utilise near infrared excitation.

Covalent Attachment of Active Enzymes to Upconversion Phosphors Allows Ratiometric Detection of Substrates.

Upconverting phosphors (UCPs) convert multiple low energy photons into higher energy emission via the process of photon upconversion and offer an attractive alternative to organic fluorophores for use as luminescent probes. Here, UCPs were capped with functionalized silica in order to provide a surface to covalently conjugate proteins with surface-accessible cysteines. Variants of green fluorescent protein (GFP) and the flavoenzyme pentaerythritol tetranitrate reductase (PETNR) were then attached via maleimide-thiol coupling in order to allow energy transfer from the UCP to the GFP or flavin cofactor of PETNR, respectively.

Observation of the Δg mechanism resulting from the ultrafast spin dynamics that follow the photolysis of coenzyme B.

Throughout nature, both free radicals and transient radical reaction intermediates are vital to many biological functions. Coenzyme B is a case in point. This organometallic cofactor generates a radical pair upon activation in its dependent enzymes by substrate binding and following photolysis.

Photochemical Spin Dynamics of the Vitamin B Derivative, Methylcobalamin.

Derivatives of vitamin B are six-coordinate cobalt corrinoids found in humans, other animals, and microorganisms. By acting as enzymatic cofactors and photoreceptor chromophores, they serve vital metabolic and photoprotective functions. Depending on the context, the chemical mechanisms of the biologically active derivatives of B-methylcobalamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl)-can be very different from one another.

Evaluating spectral overlap with the degree of quenching in UCP luminescence energy transfer systems.

The use of organic-based fluorophores has been firmly established as a key tool in the biological sciences, with many biological-sensing methods taking advantage of Förster Resonance Energy Transfer (FRET) between different fluorescent organic-based dyes following one photon excitation. Nevertheless, the employment of UV-visible absorbing dyes as fluorescent tags and markers typically suffer from several drawbacks including relatively high energy of excitation wavelength, photobleaching and competitive autofluorescence, which often limit their effectiveness and longevity both in vitro and in vivo. As an alternative, lanthanide-doped upconverting phosphors (UCP) have emerged as a new class of materials for use in optical imaging and FRET sensing; they exhibit high photo- and chemical stability and utilise near infrared (nIR) excitation.

Native mass spectrometry reveals the conformational diversity of the UVR8 photoreceptor.

UVR8 is a plant photoreceptor protein that regulates photomorphogenic and protective responses to UV light. The inactive, homodimeric state absorbs UV-B light, resulting in dissociation into monomers, which are considered to be the active state and comprise a β-propeller core domain and intrinsically disordered N- and C-terminal tails. The C terminus is required for functional binding to signaling partner COP1.

Two photon spectroscopy and microscopy of the fluorescent flavoprotein, iLOV.

LOV-domains are ubiquitous photosensory proteins that are commonly re-engineered to serve as powerful and versatile fluorescent proteins and optogenetic tools. The photoactive, flavin chromophore, however, is excited using short wavelengths of light in the blue and UV regions, which have limited penetration into biological samples and can cause photodamage. Here, we have used non-linear spectroscopy and microscopy of the fluorescent protein, iLOV, to reveal that functional variants of LOV can be activated to great effect by two non-resonant photons of lower energy, near infrared light, not only in solution but also in biological samples.

A Green-Light-Responsive System for the Control of Transgene Expression in Mammalian and Plant Cells.

The ever-increasing complexity of synthetic gene networks and applications of synthetic biology requires precise and orthogonal gene expression systems. Of particular interest are systems responsive to light as they enable the control of gene expression dynamics with unprecedented resolution in space and time. While broadly used in mammalian backgrounds, however, optogenetic approaches in plant cells are still limited due to interference of the activating light with endogenous photoreceptors.

The photochemistry and photobiology of vitamin B.

Biologically active derivatives of vitamin B are organometallic cobalt-corrinoid complexes crucial for the healthy function of humans, animals and microbes. Their role as cofactors to numerous, thermally-driven metabolic enzymes is well described, and varies depending on the nature of the upper axial ligand. This ligand also significantly influences the photophysics and photochemistry of B.

Vertebrate Cryptochromes are Vestigial Flavoproteins.

All cryptochromes are currently classified as flavoproteins. In animals their best-described role is as components of the circadian clock. This circadian function is variable, and can be either light-dependent or -independent; the molecular origin of this difference is unknown.

Direct Evidence of an Excited-State Triplet Species upon Photoactivation of the Chlorophyll Precursor Protochlorophyllide.

The chlorophyll precursor protochlorophyllide (Pchlide), which is the substrate for the light-driven enzyme protochlorophyllide oxidoreductase, has unique excited-state properties that facilitate photocatalysis. Previous time-resolved spectroscopy measurements have implied that a long-lived triplet state is formed during the excited-state relaxation of Pchlide, although direct evidence of its existence is still lacking. Here we use time-resolved electron paramagnetic resonance (EPR) in combination with time-resolved absorption measurements at a range of temperatures (10-290 K), solvents, and oxygen concentrations to provide a detailed characterization of the triplet state of Pchlide.