Investigation of studies for cytochrome P450 isoforms specificity.

Cytochrome P450 (CYP450) enzymes comprise a highly diverse superfamily of heme-thiolate proteins that responsible for catalyzing over 90 % of enzymatic reactions associated with xenobiotic metabolism in humans. Accurately predicting whether chemicals are substrates or inhibitors of different CYP450 isoforms can aid in pre-selecting hit compounds for the drug discovery process, chemical toxicology studies, and patients treatment planning. In this work, we investigated studies on CYP450s specificity over past twenty years, categorizing these studies into structure-based and ligand-based approaches.

Discovery and characterization of a new class of NAD-independent SIRT1 activators.

The activity of sirtuin 1 (SIRT1, a member of the NAD-dependent deacetylases family) decreases during aging as NAD levels naturally decline, thus increasing the risk of several age-associated diseases. Several sirtuin-activating compounds (STACs) have been developed to counteract the age-associated reduction in SIRT1 activity, and some of them are currently under development in clinical trials. STACs induce SIRT1 activation, either through allosteric activation of the enzyme in the presence of NAD, or by increasing NAD levels by inhibiting its degradation or by supplying a key precursor in biosynthesis.

Atomistic description of the OCTN1 recognition mechanism via in silico methods.

The Organic Cation Transporter Novel 1 (OCTN1), also known as SLC22A4, is widely expressed in various human tissues, and involved in numerous physiological and pathological processes remains. It facilitates the transport of organic cations, zwitterions, with selectivity for positively charged solutes. Ergothioneine, an antioxidant compound, and acetylcholine (Ach) are among its substrates.

In Silico Description of the Direct Inhibition Mechanism of Endothelial Lipase by ANGPTL3.

Angiopoietin-like protein 3 (ANGPTL3) is a plasmatic protein that plays a crucial role in lipoprotein metabolism by inhibiting the lipoprotein lipase (LPL) and the endothelial lipase (EL) responsible for the hydrolysis of phospholipids on high-density lipoprotein (HDL). Interest in developing new pharmacological therapies aimed at inhibiting ANGPTL3 has been growing due to the hypolipidemic and antiatherogenic profile observed in its absence. The goal of this study was the in silico characterization of the interaction between ANGPTL3 and EL.

GM1 structural requirements to mediate neuronal functions.

Since the 1980s, it has been known that the administration of ganglioside GM1 to cultured cells induced or enhanced neuronal differentiation. GM1 mechanism of action relies on its direct interaction and subsequent activation of the membrane tyrosine kinase receptor, TrkA, which naturally serves as NGF receptor. This process is mediated by the sole oligosaccharide portion of GM1, the pentasaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc.

SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability.

Innervation of the hypothalamic median eminence by Gonadotropin-Releasing Hormone (GnRH) neurons is vital to ensure puberty onset and successful reproduction. However, the molecular and cellular mechanisms underlying median eminence development and pubertal timing are incompletely understood. Here we show that Semaphorin-6A is strongly expressed by median eminence-resident oligodendrocytes positioned adjacent to GnRH neuron projections and fenestrated capillaries, and that Semaphorin-6A is required for GnRH neuron innervation and puberty onset.

Healing from weight stigma in community: A thematic analysis of a group intervention for large-bodied individuals.

Discrimination against and negative beliefs about large-bodied individuals, known as weight stigma, is pervasive and harmful. While previous research has focused on the negative consequences of weight stigma, the present study aims to highlight the lived experience of large-bodied individuals while also exploring the process of healing from harmful experiences of weight stigma. Ten adult (9/10 White, 8/10 cisgender women), large-bodied individuals recruited via snowball sampling through a nonprofit, grassroots, eating disorder advocacy organization participated in a 10-week, counselor-facilitated support group with the shared goal of healing from the impact of weight stigma.

Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder.

Purpose: RPH3A encodes a protein involved in the stabilization of GluN2A subunit of N-methyl-D-aspartate (NMDA)-type glutamate receptors at the cell surface, forming a complex essential for synaptic plasticity and cognition. We investigated the effect of variants in RPH3A in patients with neurodevelopmental disorders.

Methods: By using trio-based exome sequencing, GeneMatcher, and screening of 100,000 Genomes Project data, we identified 6 heterozygous variants in RPH3A.

Amyposomes, a nanotechnological chaperone with anti-amyloidogenic activity.

Aim: The effect of liposomes bi-functionalized with phosphatidic acid and with a synthetic peptide derived from human apolipoprotein E has been evaluated on the aggregation features of different amyloidogenic proteins: human Amyloid β1-40 (Aβ), transthyretin (TTR) variant S52P, human β2microglobulin (β2m) variants ΔN6 and D76N, Serum Amyloid A (SAA).

Methods: The formation of fibrillar aggregates of the proteins was investigated by ThioflavinT fluorescence assay and validated by Atomic Force Microscopy.

Results: The results show that liposomes are preventing the transition of non-aggregated forms to the fibrillar state, with stronger effects on Aβ, β2m ΔN6 and SAA.

Effect of Fc core fucosylation and light chain isotype on IgG1 flexibility.

N-glycosylation plays a key role in modulating the bioactivity of monoclonal antibodies (mAbs), as well as the light chain (LC) isotype can influence their physicochemical properties. However, investigating the impact of such features on mAbs conformational behavior is a big challenge, due to the very high flexibility of these biomolecules. In this work we investigate, by accelerated molecular dynamics (aMD), the conformational behavior of two commercial immunoglobulins G1 (IgG1), representative of κ and λ LCs antibodies, in both their fucosylated and afucosylated forms.

The diachronic trend of female and male stature in Milan over 2000 years.

Stature is a biological trait directly determined by the interaction of genetic and environmental components. As such, it is often evaluated as an indicator for the reconstruction of skeletal biological profiles, past health, and social dynamics of human populations. Based on the analysis of 549 skeletons from the CAL (Collezione Antropologica LABANOF), a study of the diachronic trend of male and female adult stature in Milan (Italy) is being proposed here, covering a time span of about 2000 years, ranging from the Roman era to present-days.

Exploration of Novel Scaffolds Targeting Cytochrome of .

The fulfilment of the European "Farm to Fork" strategy requires a drastic reduction in the use of "at risk" synthetic pesticides; this exposes vulnerable agricultural sectors-among which is the European risiculture-to the lack of efficient means for the management of devastating diseases, thus endangering food security. Therefore, novel scaffolds need to be identified for the synthesis of new and more environmentally friendly fungicides. In the present work, we employed our previously developed 3D model of cytochrome (cyt ) complex to perform a high-throughput virtual screening of two commercially available compound libraries.

Functional Heterodimerization between the G Protein-Coupled Receptor GPR17 and the Chemokine Receptors 2 and 4: New Evidence.

GPR17, a G protein-coupled receptor, is a pivotal regulator of myelination. Its endogenous ligands trigger receptor desensitization and downregulation allowing oligodendrocyte terminal maturation. In addition to its endogenous agonists, GPR17 could be promiscuously activated by pro-inflammatory oxysterols and chemokines released at demyelinating lesions.

In silico investigation on structure-function relationship of members belonging to the human SLC52 transporter family.

Riboflavin is an essential water-soluble vitamin that needs to be provided through the diet because of the conversion into flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), important cofactors in hundreds of flavoenzymes. The adsorption and distribution of riboflavin is mediated by transmembrane transporters of the SLC52 family, namely RFVT1-3, whose mutations are mainly associated with two diseases, MADD and the Brown-Vialetto-Van Laere syndrome. Interest in RFVTs as pharmacological targets has increased in the last few years due to their overexpression in several cancer cells, which can be exploited both by blocking the uptake of riboflavin into the cancerous cells, and by performing cancer targeted delivery of drugs with a high affinity for RFVTs.

Rabphilin-3A as a novel target to reverse α-synuclein-induced synaptic loss in Parkinson's disease.

Toxic aggregates of α-synuclein (αsyn) are considered key drivers of Parkinson's disease (PD) pathology. In early PD, αsyn induces synaptic dysfunction also modulating the glutamatergic neurotransmission. However, a more detailed understanding of the molecular mechanisms underlying αsyn-triggered synaptic failure is required to design novel therapeutic interventions.

Molecular Modelling of NONO and SFPQ Dimerization Process and RNA Recognition Mechanism.

NONO and SFPQ are involved in multiple nuclear processes (e.g., pre-mRNA splicing, DNA repair, and transcriptional regulation).

Contralateral Forced Eyelid Closure Increases Intraocular Pressure.

Objectives: The purpose of the study was to describe the influence of contralateral forced eyelid closure on intraocular pressure (IOP).

Methods: Twenty-one healthy volunteers with no ophthalmic history had their IOP measured in the supine position to simulate the intraoperative environment. Intraocular pressure was measured with a handheld tonometer over three scenarios: (1) both eyes in a relaxed state, (2) eyelid speculum in the right eye with both eyes open and relaxed, (3) eyelid speculum in the right eye with the fellow eye squeezing tightly.

"From Protein Toxins to Applied Toxicological Testing" virtual workshop identifies the need for a bioinformatic framework to assess novel food protein safety.

On October 21-22, 2020 the HESI (Health and Environmental Sciences Institute) Protein Allergens, Toxins, and Bioinformatics Committee, and the Society of Toxicology Food Safety Specialty Section co-hosted a virtual workshop titled "From Protein Toxins to Applied Toxicological Testing". The workshop focused on the safety assessment of novel proteins contained in foods and feeds, was globally represented by over 200 stakeholder attendees, and featured contributions from experts in academia, government and non-government organizations, and agricultural biotechnology developers from the private sector. A range of topics relevant to novel protein safety were discussed, including: the state of protein toxin biology, modes and mechanisms of action, structures and activity, use of bioinformatic analyses to assess the safety of a protein, and ways to leverage computational biology with in silico approaches for protein toxin identification/characterization.

Insect Fungus Metarhizium robertsii Is a Rare Causative Agent of Keratitis.

Purpose: This study aimed to describe a case of keratitis secondary to Metarhizium robertsii, a soil-dwelling fungus with typical insect pathogenicity.

Methods: A Case report.

Results: A 58-year-old man with a ocular history of soft contact lens overwear, poor contact lens hygiene, and ocular exposure to ground well water supplying his house was referred to our university practice for a central corneal ulcer with 40% thinning.

Sterile iris abscess associated with herpes zoster ophthalmicus.

Purpose: To report a case of a sterile iris abscess associated with herpes zoster ophthalmicus (HZO).

Observations: A 69-year-old African American female presented to SUNY Downstate Medical Center complaining of left-sided eye pain for two weeks. The patient had a best-corrected visual acuity of 20/30 OD and 20/200 OS.

Hemolymph proteins: An overview across marine arthropods and molluscs.

In this compilation we collect information about the main protein components in hemolymph and stress the continued interest in their study. The reasons for such an attention span several areas of biological, veterinarian and medical applications: from the notions for better dealing with the species - belonging to phylum Arthropoda, subphylum Crustacea, and to phylum Mollusca - of economic interest, to the development of 'marine drugs' from the peptides that, in invertebrates, act as antimicrobial, antifungal, antiprotozoal, and/or antiviral agents. Overall, the topic most often on focus is that of innate immunity operated by classes of pattern-recognition proteins.

Update on corneal collagen crosslinking for ectasia.

Purpose Of Review: Corneal collagen crosslinking (CXL) is a minimally invasive treatment that can stabilize corneal ectatic disorders including keratoconus, pellucid marginal degeneration, or postrefractive surgery ectasia. The benefits of CXL have been well documented. New research is focused on modifying current treatment protocols with the goals of maximizing corneal stability while also shortening overall procedure time.

Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen .

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type , combined in some cases with promising activity against strobilurin-resistant strains.

Comparison of Clinical Features and Treatment Outcomes of Pseudomonas aeruginosa Keratitis in Contact Lens and Non-Contact Lens Wearers.

Purpose: To compare the outcomes of Pseudomonas aeruginosa keratitis (PAK) in contact lens wearers (CLWs) and non-contact lens wearers (non-CLWs) and identify risk factors for poor visual acuity (VA) outcomes in each group.

Design: Retrospective cohort study METHODS: Two hundred fourteen consecutive cases of PAK were included between January 2006 and December 2019. Clinical features, microbiologic results, and treatment course were compared between CLW and non-CLW groups.

rHDL modeling and the anchoring mechanism of LCAT activation.

Lecithin:cholesterol-acyl transferase (LCAT) plays a major role in cholesterol metabolism as it is the only extracellular enzyme able to esterify cholesterol. LCAT activity is required for lipoprotein remodeling and, most specifically, for the growth and maturation of HDLs. In fact, genetic alterations affecting LCAT functionality may cause a severe reduction in plasma levels of HDL-cholesterol with important clinical consequences.