The Mycotoxin Fumonisin B1 Induces Metabolic and Molecular Perturbations Leading to Cell Death in Arabidopsis Cell Culture

Fumonisin B1 (FB1) is a fungal toxin produced by Fusarium spp. able to exert pleiotropic toxicity in plants. FB1 is known to be a strong inducer of the programmed cell death (PCD); however, the exact mechanism underling the plant-toxin interactions and the molecular events that lead to PCD are still unclear. Therefore, in this work we provided a comprehensive investigation of the response of the model organism Arabidopsis thaliana at the nuclear, transcriptional, and biochemical level after the treatment with FB1 at two different concentrations, namely 1 and 5µM during a time-course of 96 h. FB1 induced oxidative and nitrosative bursts and a rapid cell death in Arabidopsis cell cultures, which resembled a HR-like PCD event. Different genes involved in the regulation of PCD, antioxidant metabolism, photosynthesis, resistance, and sugar transport were upregulated, especially during the late treatment time and with higher FB1 concentration. Among the antioxidant enzymes and compounds studied, only glutathione appeared to be highly induced in both treatments, suggesting that it might be an important defense molecule induced during FB1 exposure. Collectively, these findings highlight the complexity of the defense network of A. thaliana and provide important information for the understanding of the physiological, molecular, and biochemical responses to counteract FB1-induced toxicity.

Response of morphological and biochemical traits and transcriptomic of CDPKs and P5CS Genes to phytohormones and nutrients in two bread wheat germplasms under salinity conditions

Several enzymes play an important role in the biosynthesis of osmolyte in plants. The main objective of this work is to study the effects of salt stress, kinetin+potassium and giberellic acid+potassium on calcium-dependent protein kinases (CDPKs) and delta-1-pyrroline-5- carboxylate synthase (P5CS) genes expression of two bread wheat varieties. The results shodwe that, salts stress reduced the plant growth of the two wheat germplasms. Moreover, the addition of kinetin+ potassium improved the performance of morphometric parameters while the addition of giberellic acid +potassium has less effect. On the biochemical level, results indicated that salt stress increased the proline contents compared with control plants. Extra increase in proline contents was recorded by kinetin+ potassium, while the treatment of giberellic acid +potassium showed almost similar results as in salt stress only. On the molecular level, salt stress, kinetin and giberellic acid significantly increased the two genes expression of CDPKs and P5CS with more effect in presence of kinetin+ potassium.

Agrophysiological Characterization of Maize (Zea mays) Plants from EV 8728 Seeds Irradiated to Gamma Radiation

Maize (Zea mays L.) is a tropical annual herbaceous plant of the Poaceae family. It is a cereal cultivated under very varied conditions ranging from tropical to temperate climates. However, the accentuated climate change causes abiotic and biotic stresses reducing the development and the production of the plants. To improve these plants, it is important to understand the mechanisms involved in these stresses. Two doses of gamma irradiation (200 and 300 grays) were applied to the seeds of a variety (EV8728) of maize grown on an experimental plot at the Jean Lorougnon Guédé University (UJLoG). Thus, the morphological, physiological and biochemical behaviors of the plants were evaluated. The results showed that gamma radiation significantly reduces morphological parameters. However, this reduction is accentuated at 300 grays. At the physiological and biochemical level, the radiation reduced the chlorophyll a, b and total (t) contents and the carotenoid content. Additionally, the contents of proline, total protein and total sugar increased with 200 grays and decreased for 300 grays. However, the phenolic compounds content increases with the irradiation dose.

Olive Varieties under UV-B Stress Show Distinct Responses in Terms of Antioxidant Machinery and Isoform/Activity of RubisCO

In recent decades, atmospheric pollution led to a progressive reduction of the ozone layer with a consequent increase in UV-B radiation. Despite the high adaptation of olive trees to the Mediterranean environment, the progressive increase of UV-B radiation is a risk factor for olive tree cultivation. It is therefore necessary to understand how high levels of UV-B radiation affect olive plants and to identify olive varieties which are better adapted. In this study we analyzed two Italian olive varieties subjected to chronic UV-B stress. We focused on the effects of UV-B radiation on RubisCO, in terms of quantity, enzymatic activity and isoform composition. In addition, we also analyzed changes in the activity of antioxidant enzymes (SOD, CAT, GPox) to get a comprehensive picture of the antioxidant system. We also evaluated the effects of UV-B on the enzyme sucrose synthase. The overall damage at biochemical level was also assessed by analyzing changes in Hsp70, a protein triggered under stress conditions. The results of this work indicate that the varieties (Giarraffa and Olivastra Seggianese) differ significantly in the use of specific antioxidant defense systems, as well as in the activity and isoform composition of RubisCO. Combined with a different use of sucrose synthase, the overall picture shows that Giarraffa optimized the use of GPox and opted for a targeted choice of RubisCO isoforms, in addition to managing the content of sucrose synthase, thereby saving energy during critical stress points.

Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor dysfunction and cortical atrophy, independent of protein aggregation.

Background A growing body of evidence suggests that nuclear alpha-synuclein (aSyn) plays a role in the pathogenesis of Parkinson's disease (PD). However, this question has been difficult to address as controlling the localization of aSyn in experimental systems often requires protein overexpression, which results in aggregation. Methods We engineered SncaNLS mice which localize endogenous aSyn to the nucleus. We characterized these mice on a behavioral, histological, and biochemical level to determine whether the increase of nuclear aSyn is sufficient to elicit disease phenotypes. Results SncaNLS mice exhibit age-dependent motor deficits and altered gastrointestinal function. We found that these phenotypes were not linked to aSyn aggregation or phosphorylation. Through histological analyses, we observed motor cortex atrophy in the absence of midbrain dopaminergic neurodegeneration. We sampled cortical proteomes of SncaNLS mice and controls to determine the molecular underpinnings of these pathologies. Interestingly, we found several dysregulated proteins involved in dopaminergic signaling, namely Darpp-32, which we further confirmed was decreased in cortical samples of the SncaNLS mice compared to controls via immunoblotting. Conclusions These results suggest that chronic endogenous nuclear aSyn can elicit toxic phenotypes in mice, independent of its aggregation. This model raises key questions related to the mechanism of aSyn toxicity in PD and provides a new model to study an underappreciated aspect of PD pathogenesis.

Hydrolysis of a second Asp-Pro site at the N-terminus of NOTCH3 in inherited vascular dementia

Cerebrovascular pathology at the biochemical level has been informed by the study of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a vascular disorder caused by NOTCH3 mutations. Previous work in CADASIL described N-terminal proteolysis of NOTCH3 generated by specific non-enzymatic cleavage of the first Asp-Pro sequence of the protein. Here, we investigated whether the second Asp-Pro peptide bond (residues 121–122) of NOTCH3 is cleaved in CADASIL. Monospecific antibodies were generated that recognize the neo-epitope predicted to be generated by cleavage after Asp121. These antibodies were used to localize cleavage events at Asp121 in post-mortem CADASIL and control brain tissue and to investigate factors that regulate cleavage at Asp121. We report that cleavage at Asp121 occurs at a high level in the arterial media of CADASIL cerebral arteries. Leptomeningeal arteries demonstrated substantially more cleavage product than penetrating arteries in the white matter, and control vessels harbored only a small amount of cleaved NOTCH3. Proteolysis at Asp121 occurred in purified preparations of NOTCH3 ectodomain, was increased by acidic pH and reductive conditions, and required native protein conformation for cleavage. Increasing the concentration of NOTCH3 EGF-like domain protein elevated the level of proteolysis. On the other hand, several polyanionic chemicals potently blocked cleavage at Asp121. These studies demonstrate that the NOTCH3 protein in CADASIL is cleaved in multiple locations at labile Asp-Pro peptide bonds. As such, chronic brain vascular disease, like other neurodegenerative conditions, features proteolysis of pathological proteins at multiple sites which may generate small pathological peptides.

Nanoparticles in traumatic spinal cord injury: therapy and diagnosis

Nanotechnology has been previously employed for constructing drug delivery vehicles, biosensors, solar cells, lubricants and as antimicrobial agents. The advancement in synthesis procedure makes it possible to formulate nanoparticles (NPs) with precise control over physico-chemical and optical properties that are desired for specific clinical or biological applications. The surface modification technology has further added impetus to the specific applications of NPs by providing them with desirable characteristics. Hence, nanotechnology is of paramount importance in numerous biomedical and industrial applications due to their biocompatibility and stability even in harsh environments. Traumatic spinal cord injuries (TSCIs) are one of the major traumatic injuries that are commonly associated with severe consequences to the patient that may reach to the point of paralysis. Several processes occurring at a biochemical level which exacerbate the injury may be targeted using nanotechnology. This review discusses possible nanotechnology-based approaches for the diagnosis and therapy of TSCI, which have a bright future in clinical practice.

Drug-Induced Photosensitivity—From Light and Chemistry to Biological Reactions and Clinical Symptoms

Photosensitivity is one of the most common cutaneous adverse drug reactions. There are two types of drug-induced photosensitivity: photoallergy and phototoxicity. Currently, the number of photosensitization cases is constantly increasing due to excessive exposure to sunlight, the aesthetic value of a tan, and the increasing number of photosensitizing substances in food, dietary supplements, and pharmaceutical and cosmetic products. The risk of photosensitivity reactions relates to several hundred externally and systemically administered drugs, including nonsteroidal anti-inflammatory, cardiovascular, psychotropic, antimicrobial, antihyperlipidemic, and antineoplastic drugs. Photosensitivity reactions often lead to hospitalization, additional treatment, medical management, decrease in patient’s comfort, and the limitations of drug usage. Mechanisms of drug-induced photosensitivity are complex and are observed at a cellular, molecular, and biochemical level. Photoexcitation and photoconversion of drugs trigger multidirectional biological reactions, including oxidative stress, inflammation, and changes in melanin synthesis. These effects contribute to the appearance of the following symptoms: erythema, swelling, blisters, exudation, peeling, burning, itching, and hyperpigmentation of the skin. This article reviews in detail the chemical and biological basis of drug-induced photosensitivity. The following factors are considered: the chemical properties, the influence of individual ranges of sunlight, the presence of melanin biopolymers, and the defense mechanisms of particular types of tested cells.

ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease

Despite the routine use of sandwich enzyme-linked immunosorbent assays (ELISAs) for quantifying tau levels in CSF and plasma, tau accumulations in the brains of patients with Alzheimer disease (AD) have rarely been evaluated by this method. Thus, by introducing several tau ELISAs that target different epitopes, we evaluated accumulated tau levels in postmortem brains depending on disease stage, brain areas, and other AD-related changes. Notably, tau levels in insoluble fraction determined by each ELISAs differ depending on the epitopes of antibodies: non-AD control samples yield relatively high signals when an antibody against the N-terminal region of tau is used. On the other hand, ELISAs combining antibodies against the later-middle to C-terminal regions of tau produced substantially increased signals from AD samples, compared to those from non-AD controls. Such ELISAs better distinguish AD and non-AD controls, and the results are more closely associated with Braak neurofibrillary tangles stage, Aβ accumulation, and glial markers. Moreover, these ELISAs can reflect the pattern of tau spread across brain regions. In conclusion, Tau ELISAs that combine antibodies against the later-middle to C-terminal regions of tau can better reflect neuropathological tau accumulation, which would enable to evaluate tau accumulation in the brain at a biochemical level.

Emotions as Self-Organizational Factors of Anthropogenesis, Noogenesis and Sociogenesis

Purpose. The purpose is to prove the synchronicity of anthropogenesis, noogenesis and sociogenesis based on emotions, which are their self-organizational principles, as well as to reveal the synergistic essence of these processes. Theoretical basis. The study is based on the self-organizational paradigm, the theory of autopoiesis, labour theory, pananthropological concept, as well as on the concept of synergy of biological and mental phenomena. Originality. The concept of synchronicity of anthropogenesis, noogenesis and sociogenesis based on the emotions is substantiated. The concept of self-organizational emergence of emotions on the basis of hormones is developed. It is established that anthropogenesis is a process of anthropologisation of life based on biochemical reactions in the form of hormones and emotions, which are a synergy of genetic information, biochemical processes, instincts, and physiological phenomena. It was outlined that noogenesis has an emotional dimension, because emotions are the basis for self-organization of rationality, which begins at the level of emotional consciousness. The author shows the specifics of sociogenesis, which self-organizes based on social emotions, which in their turn "distinguish" a man from the sphere of natural existence based on the ability to control emotions. Conclusions. Emotions arise self-organizationally on the basis of hormones. They are self-organizational factors of anthropogenesis, noogenesis and sociogenesis based on the synergistic effect that arises through the combination of emotions and hormones at the biochemical level. The basic principle of anthropology is emotions that synchronize anthropogenesis, noogenesis and sociogenesis, which manifests themselves on the physical, mental, and spiritual levels. At the bodily level, emotions are expressed as biochemical and hormonal reactions. At the spiritual level emotions create the basis for the development of the mind, which originates as emotional consciousness. Emotions self-organize the process of anthropologisation of life, which is possible based on the synergy of human genome, biochemical, physiological phenomena and instincts. The concepts of synchronicity of anthropogenesis, noogenesis and sociogenesis and self-organizational emergence of emotions based on hormones initiate a promising direction of further research of the role of emotions in the processes of self-organization of social phenomena.