Novel Intragenic and Genomic Variants Highlight the Phenotypic Variability in -Related Disease.

: Disruption of results in microphthalmia with linear skin lesions (MLS) characterized by microphthalmia/anophthalmia, corneal opacity, aplastic skin lesions, variable central nervous system and cardiac anomalies, intellectual disability, and poor growth in heterozygous females. Structural variants consisting of chromosomal rearrangements or deletions are the most common variant type, but a small number of intragenic variants have been reported. : Exome sequencing identified variants affecting .

A Multistep Oxidative Cascade Reaction from a Naphthalenediol-Based Pre-Ligand to a Tetranuclear Perylenequinone-Based Fe Complex.

We have developed a family of dinuclear complexes using 2,7-disubstituted 1,8-naphthalenediol ligands that bind by molecular recognition to two neighboring phosphate diesters of the DNA backbone with the dinuclear Cu and Ni complexes exhibiting a severe cytotoxicity for human cancer cells. To increase the binding affinity, we intended to synthesize the corresponding dinuclear Fe complex. Surprisingly, we obtained a tetranuclear Fe perylene-based complex instead of the expected dinuclear Fe naphthalene-based complex.

P2X7 receptor in macrophage polarization and its implications in neuroblastoma tumor behavior.

Tumor-associated macrophages (TAMs) exhibit antitumor or protumor responses related to inflammatory (or M1) and alternative (or M2) phenotypes, respectively. The P2X7 receptor plays a key role in macrophage polarization, influencing inflammation and immunosuppression. In this study, we investigated the role of the P2X7 receptor in TAMs.

Zebrafish models of human-duplicated reveal novel functions in microglia and visual system development.

The expansion of the human family, resulting in a human-specific paralog likely contributed to altered evolutionary brain features. The introduction of in mouse models is associated with changes in cortical neuronal migration, axon guidance, synaptogenesis, and sensory-task performance. Truncated SRGAP2C heterodimerizes with the full-length ancestral gene product SRGAP2A and antagonizes its functions.

In Vivo Assessment of the Pediatric Trabecular Meshwork, Schlemm Canal, and Iridocorneal Angle Using Overhead-Mounted Optical Coherence Tomography.

Purpose: To describe the in vivo morphologic characteristics of the trabecular meshwork (TM), Schlemm canal (SC), and iridocorneal angle in pediatric patients with normal eyes, glaucoma, and cataract.

Design: Prospective cohort study.

Study Population: A total of 41 children (70 eyes) were enrolled, comprising 28 normal eyes, 19 eyes with glaucoma, and 26 eyes with cataract (15 pre-, 11 post-lensectomy).

The Phosphatase RosC from Streptomyces davaonensis is Used for Roseoflavin Biosynthesis and has Evolved to Largely Prevent Dephosphorylation of the Important Cofactor Riboflavin-5'-phosphate.

The antibiotic roseoflavin is a riboflavin (vitamin B) analog. One step of the roseoflavin biosynthetic pathway is catalyzed by the phosphatase RosC, which dephosphorylates 8-demethyl-8-amino-riboflavin-5'-phosphate (AFP) to 8-demethyl-8-amino-riboflavin (AF). RosC also catalyzes the potentially cell-damaging dephosphorylation of the AFP analog riboflavin-5'-phosphate also called "flavin mononucleotide" (FMN), however, with a lower efficiency.

Chemoselective Adsorption of Allyl Ethers on Si(001): How the Interaction between Two Functional Groups Controls the Reactivity and Final Products of a Surface Reaction.

Selective adsorption of multifunctional molecules is rarely observed when the different functional groups react via nonactivated reaction channels. Although the latter is also the case for ether cleavage and the adsorption of C=C double bonds on the highly reactive Si(001) surface, we find that allyl ethers, which combine both functional groups, react on Si(001) selectively via the cleavage of the molecules' ether group. In addition, our XPS measurements at 90, 150, and 300 K indicate an increased reactivity of the ether group when compared to monofunctional ethers.

Synthesis, Characterization, and Reactivity of Bispidine-Iron(IV)-Tosylimido Species.

Reported are the synthesis and detailed studies of the iron(IV)-tosylimido complexes of two isomeric pentadentate bispidine ligands (bispidines are 3,7-diazabicyclo[3.3.1]nonane derivatives).

Clinical Results of the MINIject Implant for Suprachoroidal Drainage.

This retrospective study evaluated the safety and efficacy of the new minimally invasive MINIject implant placed in the suprachoroidal space. The aim was to assess its impact on intraocular pressure (IOP) reduction and complication rate. 18 eyes from 18 patients with insufficiently controlled glaucoma received the implant using topical medications.

Increasing the electron donation in a dinucleating ligand family: molecular and electronic structures in a series of CoCo complexes.

We have developed a family of dinucleating ligands with varying terminal donors to generate dinuclear peroxo and high-valent complexes and to correlate their stabilities and reactivities with their molecular and electronic structures as a function of the terminal donors. It appears that the electron-donating ability of the terminal donors is an important handle for controlling these stabilities and reactivities. Here, we present the synthesis of a new dinucleating ligand with potentially strong donating terminal imidazole donors.

Modernizing the evaluation of infantile nystagmus: the role of handheld optical coherence tomography.

Background: Infantile nystagmus syndrome can be associated with an afferent problem (anterior or posterior segment) or constitute an isolated idiopathic disorder. With a normal ophthalmic examination, current guidelines recommend electroretinography (ERG) rather than magnetic resonance (MRI) for preliminary workup. Given the limited use of optical coherence tomography (OCT) in preverbal children, the purpose of this study was to evaluate the role of handheld OCT (HH-OCT) in the initial diagnostic evaluation of infantile nystagmus.

Impairment of adenosine signaling disrupts early embryo development: unveiling the underlying mechanisms.

Purinergic signaling has been implicated in many biological functions, including development. In this study, we investigate the functions of extracellular adenosine and adenosine receptors using a mouse embryonic stem cell (ESC) line and morula stages isolated from mouse embryos. Feeder-free mouse ESC was investigated in the absence and presence of the leukemia inhibitory factor (LIF), configuring undifferentiated cells and cells undergoing spontaneous differentiation.

Generation and Reactivity of μ-1,2-Peroxo CuCu and Bis-μ-oxo CuCu Species and Catalytic Hydroxylation of Benzene to Phenol with Hydrogen Peroxide.

Tetradentate-N ligands stabilize dinuclear {Cu(μ-1,2-peroxo)Cu} and {Cu(μ-O)Cu} species, and Cu complexes of these ligands were reported to catalyze the oxidation of benzene with HO. Here, we report {Cu(μ-1,2-peroxo)Cu} and {Cu(μ-O)Cu} intermediates of dinucleating bis(tetradentate-N) ligands depending on the absence or presence of 6-methyl substituents on the terminal pyridine donors, respectively, generated either from {CuCu} precursors with O or from {CuCu} precursors with HO and NEt. Both intermediates are not stable even at low temperatures, but they show no electrophilic HAT reactivity with DHA.

Direct and remote control of electronic structures and redox potentials in μ-oxo diferric complexes.

Non-heme diiron enzymes activate O for the oxidation of substrates in the form of peroxo FeIII2 or high-valent FeIV2 intermediates. We have developed a dinucleating bis(tetradentate) ligand system that stabilizes peroxo and hydroperoxo FeIII2 complexes with terminal 6-methylpyridine donors, while the peroxo FeIII2 intermediate is reactive with terminal pyridine donors presumably conversion to a fluent high-valent FeIV2 intermediate. We present here a derivative with electron-donating methoxy substituents at the pyridine donors and its diferric complexes with an {FeX(μ-O)FeX} (X = Cl, OAc, and OH) or an {Fe(μ-O)(μ-OAc)Fe} core.

Reactivities and Electronic Structures of μ-1,2-Peroxo and μ-1,2-Superoxo CoCo Complexes: Electrophilic Reactivity and O Release Induced by Oxidation.

Peroxo complexes are key intermediates in water oxidation catalysis (WOC). Cobalt plays an important role in WOC, either as oxides CoO or as {Co(μ1,2-peroxo)Co} complexes, which are the oldest peroxo complexes known. The oxidation of {Co(μ1,2-peroxo)Co} complexes had usually been described to form {Co(μ1,2-superoxo)Co} complexes; however, recently the formation of {Co(μ1,2-peroxo)Co} species were suggested.

Determining relative thickness of inner retinal layers on single-line foveal optical coherence tomography (OCT) in healthy pediatric eyes-normative data for handheld OCT.

Background: Handheld optical coherence tomography (HH-OCT) lacks integrated segmentation/analysis software. Optic neuropathies cause ganglion cell layer (GCL) thinning, with normal to thickened inner nuclear layer (INL), suggesting the potential value of estimating the GCL/INL ratio on single-line foveal HH-OCT scans. This study determines this ratio in macular scans from healthy eyes of young children using HH-OCT and overhead-mounted OCT.

Bj-PRO-10c, as an allosteric regulator of argininosuccinate synthase, is a potential therapy for neuroblastoma metastasis.

Cancer is a global public health issue. Neuroblastoma (NB) originates from any tissue of the sympathetic nervous system, and the most affected site is the abdomen. The adrenal gland is the primary site in 38% of cases.

Unilateral four muscle surgery for extra-large monocular exotropia.

Introduction: Recurrent exotropia is common following surgery for monocular large angle constant sensory exotropia. Surgery is usually limited to operations on the affected eye. Simultaneous oblique weakening surgery may enhance the effect of the horizontal rectus muscles surgery by decreasing the abducting forces.

Differentiated Embryonic Neurospheres from Familial Alzheimer's Disease Model Show Innate Immune and Glial Cell Responses.

Proteins involved in the Alzheimer's disease (AD), such as amyloid precursor protein (APP) and presenilin-1 (PS1), play critical roles in early development of the central nervous system (CNS), as well as in innate immune and glial cell responses. Familial AD is associated with the presence of APP and PS1 mutations. However, it is still unknown whether these mutations cause deficits in CNS development of carriers.

Neuroprotective effects of resistance physical exercise on the APP/PS1 mouse model of Alzheimer's disease.

Introduction: Physical exercise has beneficial effects by providing neuroprotective and anti-inflammatory responses to AD. Most studies, however, have been conducted with aerobic exercises, and few have investigated the effects of other modalities that also show positive effects on AD, such as resistance exercise (RE). In addition to its benefits in developing muscle strength, balance and muscular endurance favoring improvements in the quality of life of the elderly, RE reduces amyloid load and local inflammation, promotes memory and cognitive improvements, and protects the cortex and hippocampus from the degeneration that occurs in AD.

Dinuclear complex-induced DNA melting.

Dinuclear copper complexes have been designed for molecular recognition in order to selectively bind to two neighboring phosphate moieties in the backbone of double strand DNA. Associated biophysical, biochemical and cytotoxic effects on DNA were investigated in previous works, where atomic force microscopy (AFM) in ambient conditions turned out to be a particular valuable asset, since the complexes influence the macromechanical properties and configurations of the strands. To investigate and scrutinize these effects in more depth from a structural point of view, cutting-edge preparation methods and scanning force microscopy under ultra-high vacuum (UHV) conditions were employed to yield submolecular resolution images.

Binding Modes of a Cytotoxic Dinuclear Copper(II) Complex with Phosphate Ligands Probed by Vibrational Photodissociation Ion Spectroscopy.

The dinuclear copper complex bearing a 2,7-disubstituted-1,8-naphthalenediol ligand, [(HtomMe){Cu(OAc)}](OAc), a potential anticancer drug able to bind to two neighboring phosphates in the DNA backbone, is endowed with stronger cytotoxic effects and inhibition ability of DNA synthesis in human cancer cells as compared to cisplatin. In this study, the intrinsic binding ability of the charged complex [(HtomMe){Cu(OAc)}] is investigated with representative phosphate diester ligands with growing chemical complexity, ranging from simple inorganic phosphate up to mononucleotides. An integrated method based on high-resolution mass spectrometry (MS), tandem MS, and infrared multiple photon dissociation (IRMPD) spectroscopy in the 600-1800 cm spectral range, backed by quantum chemical calculations, has been used to characterize complexes formed in solution and delivered as bare species by electrospray ionization.