Spontaneously Immortalised Nonhuman Primate Müller Glia Cell Lines as Source to Explore Retinal Reprogramming Mechanisms for Cell Therapies.

Cell replacement therapies for ocular diseases characterised by photoreceptors degeneration are challenging due to poor primary cell survival in culture. A stable retinal cell source to replace lost photoreceptors holds promise. Müller glia cells play a pivotal role in retinal homoeostasis by providing metabolic and structural support to retinal neurons, preventing aberrant photoreceptors migration, and facilitating safe glutamate uptake.

The Collector Hypothesis : Who Benefits More from Art, the Artist or the Collector?

Human fascination with art has deep evolutionary roots, yet its role remains a puzzle for evolutionary theory. Although its widespread presence across cultures suggests a potential adaptive function, determining its evolutionary origins requires more comprehensive evidence beyond mere universality or assumed survival benefits. This paper introduces and tests the Collector Hypothesis, which suggests that artworks serve as indicators of collectors' surplus wealth and social status, offering greater benefits to collectors than to artists in mating and reproductive contexts.

Mechanistic investigations of the Fe(ii) mediated synthesis of squaraines.

The scission and homologation of CO is a fundamental process in the Fischer-Tropsch reaction. However, given the heterogeneous nature of the catalyst and forcing reaction conditions, it is difficult to determine the intermediates of this reaction. Here we report detailed mechanistic insight into the scission/homologation of CO by two-coordinate iron terphenyl complexes.

Cleaved TMEM106B forms amyloid aggregates in central and peripheral nervous systems.

Filaments made of residues 120-254 of transmembrane protein 106B (TMEM106B) form in an age-dependent manner and can be extracted from the brains of neurologically normal individuals and those of subjects with a variety of neurodegenerative diseases. TMEM106B filament formation requires cleavage at residue 120 of the 274 amino acid protein; at present, it is not known if residues 255-274 form the fuzzy coat of TMEM106B filaments. Here we show that a second cleavage appears likely, based on staining with an antibody raised against residues 263-274 of TMEM106B.

What is occlusion? Part 2.

Some dentists choose to ignore the subject of occlusion, while others propose a set of doctrinal rules. It is of little wonder therefore that it can become a source of confusion and even controversy. This series of two papers aims, firstly, to answer the very simple question of 'what is occlusion?'.

What is occlusion? Part 1.

Some dentists choose to ignore the subject of occlusion, while others propose a set of doctrinal rules. It is of little wonder therefore that it can become a source of confusion and even controversy. This series of two papers aims, firstly, to answer the very simple question of 'what is occlusion?'.

Sensing the Spin State of Room-Temperature Switchable Cyanometallate Frameworks with Nitrogen-Vacancy Centers in Nanodiamonds.

Room-temperature magnetically switchable materials play a vital role in current and upcoming quantum technologies, such as spintronics, molecular switches, and data storage devices. The increasing miniaturization of device architectures produces a need to develop analytical tools capable of precisely probing spin information at the single-particle level. In this work, we demonstrate a methodology using negatively charged nitrogen vacancies (NV) in fluorescent nanodiamond (FND) particles to probe the magnetic switching of a spin crossover (SCO) metal-organic framework (MOF), [Fe(1,6-naphthyridine)(Ag(CN))] material (), and a single-molecule photomagnet [X(18-crown-6)(HO)]Fe(CN)·2HO, where X = Eu and Dy (materials and , respectively), in response to heat, light, and electron beam exposure.

Constructing the brief diagnostic criteria for temporomandibular disorders (bDC/TMD) for field testing.

Background: Despite advances in temporomandibular disorders' (TMDs) diagnosis, the diagnostic process continues to be problematic in non-specialist settings.

Objective: To complete a Delphi process to shorten the Diagnostic Criteria for TMD (DC/TMD) to a brief DC/TMD (bDC/TMD) for expedient clinical diagnosis and initial management.

Methods: An international Delphi panel was created with 23 clinicians representing major specialities, general dentistry and related fields.

β-Peptides incorporating polyhydroxylated cyclohexane β-amino acid: synthesis and conformational study.

We describe the synthesis of trihydroxylated cyclohexane β-amino acids from (-)-shikimic acid, in their and configuration, and the incorporation of the isomer into a -2-aminocyclohexanecarboxylic acid peptide chain. Subsequently, the hydroxyl groups were partially or totally deprotected. The structural study of the new peptides by FTIR, CD, solution NMR and DFT calculations revealed that they all fold into a 14-helix secondary structure, similarly to the homooligomer of -2-aminocyclohexanecarboxylic acid.

Developmental Expression of the Cell Cycle Regulator p16 in Retinal Glial Cells: A Novel Marker for Immature Ocular Astrocytes?

Retinal astrocytes are vital for neuronal homeostasis in the retina. Together with Müller glia, they provide retinal cells with neurotrophic factors, antioxidative support, and defense mechanisms such as the formation of the blood-retinal barrier. Substantial heterogeneity of astrocyte morphology and function represents a challenge for identification of distinct subtypes which may be potential targets for therapeutic purposes.

Phenotypic screening identifies a trisubstituted imidazo[1,2-a]pyridine series that induces differentiation in multiple AML cell lines.

Acute myeloid leukaemia (AML) is an aggressive type of leukaemia with low rates of long-term survival. While the current standard of care is based on cytotoxic chemotherapy, a promising emerging approach is differentiation therapy. However, most current differentiating agents target specific mutations and are effective only in certain patient subtypes.

General Approach to Enantiopure 1-Aminopyrrolizidines: Application to the Asymmetric Synthesis of the Loline Alkaloids.

The synthesis of a range of loline alkaloids is reported. The C(7) and C(7a) stereogenic centers for the targets were formed by the established conjugate addition of lithium ()--benzyl--(α-methylbenzyl)amide to -butyl 5-benzyloxypent-2-enoate, ensuing enolate oxidation to give an α-hydroxy-β-amino ester, and then formal exchange of the resultant amino and hydroxyl functionalities (via the intermediacy of the corresponding aziridinium ion) to give an α-amino-β-hydroxy ester. Subsequent transformation gave a 3-hydroxyprolinal derivative which was converted to the corresponding --butylsulfinylimine.

Relationships between tooth wear, bruxism and temporomandibular disorders.

This article will provide an overview of the diagnosis of common temporomandibular disorders (TMDs) and bruxism, along with their relevance in management of tooth wear. When assessing and managing a tooth wear case, the teeth should not be considered in isolation, but as part of the articulatory system, which has three inter-related elements: the teeth, the temporomandibular joints and the masticatory muscles. The presence/absence of bruxism and TMD are highly relevant, although there may not be a causal relationship between these.

Self-assembly of chiral diketopyrrolopyrrole chromophores giving supramolecular chains in monolayers and twisted microtapes.

Chiral diketopyrrolopyrroles appended with enantiomeric ethyl lactate functions through an ether linkage to the aryl backbone of the chromophore were synthesized via the Mitsunobu reaction. The molecules have good solubility and excellent optical properties, high molar absorption coefficients, and fluorescence quantum yields. Helical aggregates with circular dichroism arising from the supramolecular arrangement are seen in both solution and thin films, and the aggregates also display circularly polarized luminescence (g  ≈ ±0.

Increase in Tau Pathology in P290S Knock-In Mice Crossed with Mice.

Alzheimer's Disease (AD) is characterized by the pathologic assembly of amyloid β (Aβ) peptide, which deposits into extracellular plaques, and tau, which accumulates in intraneuronal inclusions. To investigate the link between Aβ and tau pathologies, experimental models featuring both pathologies are needed. We developed a mouse model featuring both tau and Aβ pathologies by knocking the P290S mutation into murine and crossing these knock-in (KI) mice with the KI line.

Highly electron deficient diketopyrrolopyrroles.

The synthesis, spectroelectrochemical and structural characteristics of highly electron-accepting diketopyrrrolopyrrole (DPP) molecules with adjoining pyridinium rings is reported, along with an assessment of their toxicity, which is apparently low. The compounds show reversible electrochemistry and in one subfamily a massive increase in molar extinction coefficient upon electrochemical reduction.

Donor-Acceptor Dyads and Triads Employing Core-Substituted Naphthalene Diimides: A Synthetic and Spectro (Electrochemical) Study.

Donor-acceptor dyads and triads comprising core-substituted naphthalene diimide (NDI) chromophores and either phenothiazine or phenoxazine donors are described. Synthesis combined with electrochemical and spectroelectrochemical investigations facilitates characterisation of the various redox states of these molecules, confirming the ability to combine arrays of electron donating and accepting moieties into single species that retain the redox properties of these individual moieties.

Slow magnetic relaxation in Fe(II) -terphenyl complexes.

Two-coordinate transition metal complexes are exciting candidates for single-molecule magnets (SMMs) because their highly axial coordination environments lead to sizeable magnetic anisotropy. We report a series of five structurally related two-coordinate Fe(II) -terphenyl complexes (4-R-2,6-XylCH)Fe [R = Bu (1), SiMe (2), H (3), Cl (4), CF (5)] where, by changing the functionalisation of the -substituent (R), we alter their magnetic function. All five complexes are field-induced single-molecule magnets, with relaxation rates that are well-described by a combination of direct and Raman mechanisms.

A tubulin binding molecule drives differentiation of acute myeloid leukemia cells.

Despite much progress in developing better drugs, many patients with acute myeloid leukemia (AML) still die within a year of diagnosis. This is partly because it is difficult to identify therapeutic targets that are effective across multiple AML subtypes. One common factor across AML subtypes is the presence of a block in differentiation.

Evaluating the efficacy and safety of a novel prophylactic nasal spray in the prevention of SARS-CoV-2 infection: A multi-centre, double blind, placebo-controlled, randomised trial.

Background The COVID-19 pandemic continues to devastate communities all over the world. The aim of this study was to evaluate the efficacy and safety of the test agent as a prophylaxis against SARS-CoV-2 infection in a population of high-risk healthcare workers. Methods The study was a multi-centre, prospective, double blind, randomized, placebo-controlled trial.

Structure-activity relationships of 2-pyrimidinecarbohydrazides as utrophin modulators for the potential treatment of Duchenne muscular dystrophy.

A therapeutic approach that holds the potential to treat all Duchenne muscular dystrophy (DMD) patient populations is utrophin modulation. Ezutromid, a first generation utrophin modulator which was later found to act via antagonism of the arylhydrocarbon receptor, progressed to Phase 2 clinical trials. Although interim data showed target engagement and functional improvements, ezutromid ultimately failed to meet its clinical endpoints.

Microgrewiapine C: Asymmetric Synthesis, Spectroscopic Data, and Configuration Assignment.

The first asymmetric synthesis of microgrewiapine C, a piperidine alkaloid isolated from , is reported. This synthesis prompted correction of the H and C NMR data for the natural sample of the alkaloid, which was achieved by reanalysis of the original spectra. The corrected data for the natural product were found to be identical to those of the synthetic sample prepared herein, thus confirming the structural and relative configurational assignment of microgrewiapine C.