Investigating the self-assembly of 2NapFF and ureido-pyrimidinone multicomponent systems for cell culture.

Low molecular weight gels are formed the self-assembly of small molecules into fibrous structures. In the case of hydrogels, these networks entrap large volumes of water, yielding soft materials. Such gels tend to have weak mechanical properties and a high permeability for cells, making them particularly appealing for regenerative medicine applications.

Vascular mechanisms of post-COVID-19 conditions: Rho-kinase is a novel target for therapy.

Background: In post-coronavirus disease-19 (post-COVID-19) conditions (long COVID), systemic vascular dysfunction is implicated, but the mechanisms are uncertain, and the treatment is imprecise.

Methods And Results: Patients convalescing after hospitalization for COVID-19 and risk factor matched controls underwent multisystem phenotyping using blood biomarkers, cardiorenal and pulmonary imaging, and gluteal subcutaneous biopsy (NCT04403607). Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics.

Physical activity and fat-free mass during growth and in later life.

Background: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.

Objectives: A study is presented of the association between FFM and physical activity in relation to age.

Methods: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database.

Time-Domain Line-Shape Analysis from 2D Spectroscopy to Precisely Determine Hamiltonian Parameters for a Photosynthetic Complex.

Optical signals come from coherences between quantum states, with spectral line widths determined by the coherences' dephasing dynamics. Using a 2D electronic spectrometer, we observe weak coherence- and rephasing-time-domain signals persisting to 1 ps in the Fenna-Matthews-Olson complex at 77 K. These are coherences between the ground and excited states prepared after the complex interacts once or three times with light, rather than zero-quantum coherences that are more frequently investigated following two interactions.

Nanopatterned Titanium Implants Accelerate Bone Formation In Vivo.

Accelerated de novo formation of bone is a highly desirable aim of implants targeting musculoskeletal injuries. To date, this has primarily been addressed by biologic factors. However, there is an unmet need for robust, highly reproducible yet economic alternative strategies that strongly induce an osteogenic cell response.

Pushing the Photon Limit: Nanoantennas Increase Maximal Photon Stream and Total Photon Number.

Nanoantennas are well-known for their effective role in fluorescence enhancement, both in excitation and emission. Enhancements of 3-4 orders of magnitude have been reported. Yet in practice, the photon emission is limited by saturation due to the time that a molecule spends in singlet and especially triplet excited states.

Lake bathymetry and species occurrence predict the distribution of a lacustrine apex predator.

This study examined the abiotic and biotic characteristics of ecosystems that allow expression of a life history called ferox trout, the colloquial name given to brown trout Salmo trutta adopting a piscivorous life history strategy, an apex predator in post-glacial lakes in northern Europe. One hundred and ninety-two lakes in Scotland show evidence of currently, or historically, supporting ferox S. trutta; their presence was predicted in logistic models by larger and deeper lakes with a large catchment that also support populations of Arctic charr Salvelinus alpinus.

Dark States in the Light-Harvesting complex 2 Revealed by Two-dimensional Electronic Spectroscopy.

Energy transfer and trapping in the light harvesting antennae of purple photosynthetic bacteria is an ultrafast process, which occurs with a quantum efficiency close to unity. However the mechanisms behind this process have not yet been fully understood. Recently it was proposed that low-lying energy dark states, such as charge transfer states and polaron pairs, play an important role in the dynamics and directionality of energy transfer.

The role of ventral striatal cAMP signaling in stress-induced behaviors.

The cAMP and cAMP-dependent protein kinase A (PKA) signaling cascade is a ubiquitous pathway acting downstream of multiple neuromodulators. We found that the phosphorylation of phosphodiesterase-4 (PDE4) by cyclin-dependent protein kinase 5 (Cdk5) facilitated cAMP degradation and homeostasis of cAMP/PKA signaling. In mice, loss of Cdk5 throughout the forebrain elevated cAMP levels and increased PKA activity in striatal neurons, and altered behavioral responses to acute or chronic stressors.

Diversity of mitochondrial Ca²⁺ signaling in rat neonatal cardiomyocytes: evidence from a genetically directed Ca²⁺ probe, mitycam-E31Q.

I(Ca)-gated Ca(2+) release (CICR) from the cardiac SR is the main mechanism mediating the rise of cytosolic Ca(2+), but the extent to which mitochondria contribute to the overall Ca(2+) signaling remains controversial. To examine the possible role of mitochondria in Ca(2+) signaling, we developed a low affinity mitochondrial Ca(2+) probe, mitycam-E31Q (300-500 MOI, 48-72h) and used it in conjunction with Fura-2AM to obtain simultaneous TIRF images of mitochondrial and cytosolic Ca(2+) in cultured neonatal rat cardiomyocytes. Mitycam-E31Q staining of adult feline cardiomyocytes showed the typical mitochondrial longitudinal fluorescent bandings similar to that of TMRE staining, while neonatal rat cardiomyocytes had a disorganized tubular or punctuate appearance.

Strong antenna-enhanced fluorescence of a single light-harvesting complex shows photon antibunching.

The nature of the highly efficient energy transfer in photosynthetic light-harvesting complexes is a subject of intense research. Unfortunately, the low fluorescence efficiency and limited photostability hampers the study of individual light-harvesting complexes at ambient conditions. Here we demonstrate an over 500-fold fluorescence enhancement of light-harvesting complex 2 (LH2) at the single-molecule level by coupling to a gold nanoantenna.

Motor unit number estimation in normal and parkinsonism model of medial gastrocnemius muscle in rats.

Motor units (MUs) reflect the function of the central nervous motor system. Thus, the estimated MU number is a good option to investigate the functional movement disorder in the Parkinson's disease (PD). The purpose of this study was to compare the estimated MUs number in the medial gastrocnemius (MG) muscle of the normal rats and those with the parkinsonism.

Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation.

The differentiation of progenitor cells is dependent on more than biochemical signalling. Topographical cues in natural bone extracellular matrix guide cellular differentiation through the formation of focal adhesions, contact guidance, cytoskeletal rearrangement and ultimately gene expression. Osteoarthritis and a number of bone disorders present as growing challenges for our society.

Maternal testosterone influences a begging component that makes fathers work harder in chick provisioning.

In species with biparental care, parents disagree evolutionarily over the amount of care that each of them is willing to provide to offspring. It has recently been hypothesised that females may try to manipulate their mates by modifying offspring begging behaviour through yolk hormone deposition, shifting the division of labour in their own favour. To test this hypothesis we first investigated how yellow-legged gull (Larus michaellis) parents feed offspring in relation to each component of complex begging behaviour and if feeding behaviour varies between sexes.

Boldness and aggressiveness in early and late hatched three-spined sticklebacks Gasterosteus aculeatus.

Levels of boldness and the degree of aggressiveness were compared in juvenile three-spined sticklebacks Gasterosteus aculeatus that had hatched early and late in the breeding season. The most striking result found in this study was that early hatched individuals were bolder when exploring a novel environment than were late-hatched individuals. No differences in levels of aggression between early and late hatchlings were found, but a relationship between boldness and aggressiveness was present regardless of hatching date.

An aerolysin-like enterotoxin from Vibrio splendidus may be involved in intestinal tract damage and mortalities in turbot, Scophthalmus maximus (L.), and cod, Gadus morhua L., larvae.

Vibrio splendidus is a pathogen that can cause major losses during the early stages of larval turbot rearing when live feed (rotifers or Artemia) is used. As haemolytic bacteria have often been associated with larval rearing losses, we studied the role of the V. splendidus haemolysin in infection of larvae.

Long-term functional adeno-associated virus-microdystrophin expression in the dystrophic CXMDj dog.

Background: Duchenne muscular dystrophy (DMD) is a severe, inherited, muscle-wasting disorder caused by mutations in the dystrophin gene. Preclinical studies of adeno-associated virus gene therapy for DMD have been described in mouse and dog models of this disease. However, low and transient expression of microdystrophin in dystrophic dogs and a lack of long-term microdystrophin expression associated with a CD8(+)  T-cell response in DMD patients suggests that the development of improved microdystrophin genes and delivery strategies is essential for successful clinical trials in DMD patients.

Elucidation of a structural basis for the inhibitor-driven, p62 (SQSTM1)-dependent intracellular redistribution of cAMP phosphodiesterase-4A4 (PDE4A4).

A survey of PDE4 inhibitors reveals that some compounds trigger intracellular aggregation of PDE4A4 into accretion foci through association with the ubiquitin-binding scaffold protein p62 (SQSTM1). We show that this effect is driven by inhibitor occupancy of the catalytic pocket and stabilization of a "capped state" in which a sequence within the enzyme's upstream conserved region 2 (UCR2) module folds across the catalytic pocket. Only certain inhibitors cause PDE4A4 foci formation, and the structural features responsible for driving the process are defined.

Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of α1-syntrophin and α-dystrobrevin in skeletal muscles of mdx mice.

Duchenne muscular dystrophy is a severe X-linked inherited muscle wasting disorder caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vectors have been extensively used to deliver genes efficiently for dystrophin expression in skeletal muscles. To overcome limited packaging capacity of AAV vectors (<5 kb), truncated recombinant microdystrophin genes with deletions of most of rod and carboxyl-terminal (CT) domains of dystrophin have been developed.

Comparative population structure of Plasmodium malariae and Plasmodium falciparum under different transmission settings in Malawi.

Background: Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P.

The structure of the ends of α-helices in globular proteins: effect of additional hydrogen bonds and implications for helix formation.

We prepared a set of about 2000 α-helices from a relational database of high-resolution three-dimensional structures of globular proteins, and identified additional main chain i ← i+3 hydrogen bonds at the ends of the helices (i.e., where the hydrogen bonding potential is not fulfilled by canonical i ← i+4 hydrogen bonds).

Codon optimization of the microdystrophin gene for Duchene muscular dystrophy gene therapy.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting X-linked genetic disease caused by dystrophin gene mutations. Gene replacement therapy aims to transfer a functional full-length dystrophin cDNA or a quasi micro/mini-gene into the muscle. A number of AAV vectors carrying microdystrophin genes have been tested in the mdx model of DMD.

Has habitat heterogeneity promoted phenotypic and ecological sub-structuring among a Coregonus lavaretus population in a large Scottish lake?

Differences in stable-isotope values, morphology and ecology in whitefish Coregonus lavaretus were investigated between the three basins of Loch Lomond. The results are discussed with reference to a genetic investigation to elucidate any substructuring or spawning site fidelity. Foraging fidelity between basins of Loch Lomond was indicated by δ¹³C and δ¹⁵N values of C.

Response to environmental change in rainbow trout selected for divergent stress coping styles.

An extensive literature has documented differences in the way individual animals cope with environmental challenges and stressors. Two broad patterns of individual variability in behavioural and physiological stress responses are described as the proactive and reactive stress coping styles. In addition to variability in the stress response, contrasting coping styles may encompass a general difference in behavioural flexibility as opposed to routine formation in response to more subtle environmental changes and non-threatening novelties.

Unliganded structure of human bisphosphoglycerate mutase reveals side-chain movements induced by ligand binding.

Erythrocyte-specific bisphosphoglycerate mutase is a trifunctional enzyme which modulates the levels of 2,3-bisphosphoglycerate (2,3-BPG) in red blood cells by virtue of its synthase and phosphatase activities. Low levels of erythrocyte 2,3-BPG increase the affinity of haemoglobin for oxygen, thus limiting the release of oxygen into tissues. 2,3-BPG levels in stored blood decline rapidly owing to the phosphatase activity of bisphosphoglycerate mutase, which is enhanced by a fall in pH.