Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer.

Background: Poly(ADP-ribose) polymerase (PARP) is a superfamily of enzymes involved in cell survival. Both PARP1 and PARP14 are overexpressed in malignancies. No clinically approved PARP14 inhibitors are available, and PARP1 inhibitors are generally nonspecific, resulting in a need for a more diverse library of selective PARP1 and PARP14 inhibitors.

INTERACTIVE EFFECTS OF INCREASED NESTBOX TEMPERATURE AND VITAMIN E ON NESTLING GROWTH ARE ATTENUATED BY PLASTICITY IN FEMALE INCUBATION EFFORT.

In recent years, temperatures have increased globally, and nestlings of many bird species are likely regularly exposed to increased temperatures both pre- and postnatally. Even small increases in nest temperature during incubation affect offspring growth and survival in a variety of species, one cause of which is thought to be increased production of prooxidants in embryos and nestlings. Defences marshalled in response to this oxidative stress could, in turn, result in trade-offs that lead to reduced survival or growth.

loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer's Disease pathology.

The ε4 allele of apolipoprotein E () is the strongest genetic risk factor for sporadic Alzheimer's Disease (AD). Knockdown of this allele may provide a therapeutic strategy for AD, but the effect of loss-of-function (LoF) on AD pathogenesis is unknown. We searched for LoF variants in a large cohort of older controls and patients with AD and identified six heterozygote carriers of LoF variants.

The potential association between PARP14 and SARS-CoV-2 infection (COVID-19).

Understanding the potential association between the poly (ADP-ribose) polymerase member 14 (PARP14) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may aid in understanding the host immunopathological response to the virus. PARP14 has an emerging role in viral infections, and this article considers its potential mechanisms for action in either a pro- or anti-viral manner. It is evident that more experimental work is required; however, PARP14 appears vital in controlling the interferon response to the SARS-CoV-2 infection and has potential roles in balancing the proinflammatory cytokines of the cytokine storm.

family-wide profiling and 3D modelling of the poly(ADP-ribose) polymerase superfamily.

Due to the conserved nature of the poly(ADP-ribose) polymerase (PARP) catalytic domain, the identification of unique residues is critical for the design of selective inhibitors. With inhibitors of the DNA-dependent PARP members already clinically approved, new efforts lie in discovering selective inhibitors for PARP5a and beyond. Targeting the noncatalytic domains, such as the macro2 and WWE domains may also provide a way to achieve selectivity.

Design, synthesis and evaluation of potential inhibitors for poly(ADP-ribose) polymerase members 1 and 14.

Poly(ADP-ribose) polymerase (PARP) members PARP1 and PARP14 belong to an 18-member superfamily of post-translational modifying enzymes. A library of 9 novel non-NAD analog amine compounds was designed, synthesized and evaluated for inhibitory activity against PARP1 and PARP14. Both studies and assays identified compound as a potential PARP1 inhibitor, inhibiting activity by 93 ± 2% (PARP14 inhibition: 0 ± 6%), and as a potential PARP14 inhibitor, inhibiting activity by 91 ± 2% (PARP1 inhibition: 18 ± 4%), at 10-μm concentration.

Recent developments in PARP14 research.

This review aims to reflect upon the major developments in PARP14 research from late 2017 to early 2020. In doing so, this report will focus on the continual elucidation of PARP14's function including an emerging role in viral replication. This is in addition to other functional developments in cancer and inflammation, along with reflecting upon the leads in inhibitor design, including the increased attention toward the macrodomain.

From tea to treatment; epigallocatechin gallate and its potential involvement in minimizing the metabolic changes in cancer.

As the most abundant bioactive polyphenol in green tea, epigallocatechin gallate (EGCG) is a promising natural product that should be used in the discovery and development of potential drug leads. Due to its association with chemoprevention, EGCG may find a role in the development of therapeutics for prostate cancer. Natural products have long been used as a scaffold for drug design, as their already noted bioactivity can help accelerate the development of novel treatments.

Type specimens of Neuropterida in the Hope Entomological Collection, Oxford University Museum of Natural History.

The Hope Entomological Collection in the Oxford University Museum of Natural History holds a large and diverse array of historically valuable type specimens for species in the superorder Neuropterida (Megaloptera, Neuroptera, and Raphidioptera). Most are from the mid-1800s (1823-1874). Here, we report each type found during a rigorous search of the collection, and we confirm the identity and status of each type with bibliographic, specimen, and label data.

Structure, Function and Inhibition of Poly(ADP-ribose)polymerase, Member 14 (PARP14).

Poly(ADP-ribose)polymerase, member 14 (PARP14, alternatively named ARTD8, BAL2, and COAST6) is an intracellular mono(ADP-ribosyl) transferase. PARP14 transfers a negatively charged ADP-ribose unit from a donor NAD+ molecule onto a target protein, post-translationally. PARP14's domain architecture consists of three macrodomains (Macro1, Macro2 and Macro3), a WWE domain and an ARTD (or catalytic domain).

Participation of the left inferior frontal gyrus in human originality.

Human creative cognition is commonly described as a twofold cyclic process that involves an idea generation phase and an idea evaluation phase. Although the evaluation phase makes a crucial contribution to originality, its underlying mechanisms have not received sufficient research attention. Here, we suggest that the left inferior frontal gyrus (lIFG) plays a major role in the interplay between the evaluation and generation networks and that inhibiting this region's activity may have an effect on "releasing" the generation neural network, resulting in greater originality.

In vitro evaluation of the antifungal efficacy of poloxamer 407-based formulations in an infected nail plate model.

The in vitro efficacy of poloxamer 407-based formulations with antifungal ciclopirox olamine has been analysed in an infected nail plate model. As artificial nail plates, keratin films made of human hair keratin and slices from bovine hooves have been utilised. Several poloxamer 407-based formulations with 1 % active ingredient indicated complete growth inhibition of the dermatophyte fungus Trichophyton rubrum after 6days of incubation.

In vitro model of infected stratum corneum for the efficacy evaluation of poloxamer 407-based formulations of ciclopirox olamine against Trichophyton rubrum as well as differential scanning calorimetry and stability studies.

Superficial fungal skin infections are a common disease and concern 20-25% of the world's population with the dermatophyte Trichophyton rubrum being the main trigger. Due to autoinoculation, fungal skin infections of the feet (tinea pedis) often occur simultaneously with fungal nail infections (onychomycosis). Therefore, the overall objective was the development and characterisation of poloxamer 407-based formulations with the antimycotic active ingredient ciclopirox olamine (CPX) for simultaneous antifungal therapy.

In vitro permeation and penetration of ciclopirox olamine from poloxamer 407-based formulations--comparison of isolated human stratum corneum, bovine hoof plates and keratin films.

Fungal infections of skin and/or nails are common diseases resulting in major challenges in topical treatment. Therefore, the objective of the present study was to develop a dermal formulation targeting both tinea pedis and onychomycosis. The antifungal agent ciclopirox olamine (CPX) was incorporated into a variety of poloxamer 407-based formulations and analysed regarding its in vitro permeation and penetration behaviour across keratin films (KF) and bovine hoof plates as artificial nail models as well as human stratum corneum (SC).

Reconceiving autoimmunity: An overview.

Three interconnected positions are advocated: (1) although serving as a useful model, the immune self does not exist as such; (2) instead of a self/nonself demarcation, the immune system 'sees' itself, i.e., it does not ignore the 'self' or attack the 'other;' but exhibits a spectrum of responses, which when viewed from outside the system appear as discrimination of 'self' and 'nonself' based on certain criteria of reactivity.

Glaucoma progression and role of glaucoma surgery in patients with Boston keratoprosthesis.

Purpose: The aim of this study was to evaluate glaucoma onset and progression after implantation of Boston Keratoprostheses (B-KPro) and the role of glaucoma surgery.

Methods: Records of patients with B-KPro implantation during 2004 to 2009 were reviewed. Parameters relevant to B-KPro surgery and glaucoma status were recorded.

Comparison of the antifungal efficacy of terbinafine hydrochloride and ciclopirox olamine containing formulations against the dermatophyte Trichophyton rubrum in an infected nail plate model.

Onychomycosis is a fungal infection mostly induced by dermatophytes such as Trichophyton rubrum. Due to slow nail growth, the treatment takes 3-9 months depending on the nail size and infected area. Hence, high efficacy of the active ingredient without systemic side effects is of major interest.

Immunology's theories of cognition.

Contemporary immunology has established its fundamental theory as a biological expression of personal identity, wherein the "immune self" is defended by the immune system. Protection of this agent putatively requires a cognitive capacity by which the self and the foreign are perceived and thereby discriminated; from such information, discernment of the environment is achieved and activation of pathways leading to an immune response may be initiated. This so-called cognitive paradigm embeds such functions as "perception," "recognition," "learning," and "memory" to characterize immune processes, but the conceptual character of such functions has meanings that vary with the particular theory adopted.

Low-cost and readily available tissue carriers for the Boston keratoprosthesis: a review of possibilities.

The Boston keratoprosthesis (B-KPro), currently the most commonly used artificial cornea worldwide, can provide rapid visual rehabilitation for eyes with severe corneal opacities not suitable for standard corneal transplantation. However, the B-KPro presently needs a corneal graft as a tissue carrier. Although corneal allograft tissue is readily available in the United States and other developed countries with established eye banks, the worldwide need vastly exceeds supply.

In vitro and in vivo assessment of titanium surface modification for coloring the backplate of the Boston keratoprosthesis.

Purpose: Recent use of a titanium (Ti) backplate has improved the design and biocompatibility of the Boston Keratoprosthesis (BKpro). Titanium's shiny metallic appearance, however, makes the cosmetic outcome less favorable. The purpose of this study was to develop and test a coloring surface modification of Ti.

Individual and meta-immune networks.

Networks can be found everywhere-in technology, in nature and in our bodies. In this paper we present how antigen networks can be used as a model to study network interaction and architecture. Utilizing antigen microarray data of the reactivity of hundreds of antibodies of sera of ten mothers and their newborns, we reconstruct networks, either isotype specific (IgM or IgG) or person specific-mothers or newborns-and investigate the network properties.

A symbiotic view of life: we have never been individuals.

The notion of the "biological individual" is crucial to studies of genetics, immunology, evolution, development, anatomy, and physiology. Each of these biological subdisciplines has a specific conception of individuality, which has historically provided conceptual contexts for integrating newly acquired data. During the past decade, nucleic acid analysis, especially genomic sequencing and high-throughput RNA techniques, has challenged each of these disciplinary definitions by finding significant interactions of animals and plants with symbiotic microorganisms that disrupt the boundaries that heretofore had characterized the biological individual.