Generation of isogenic models of Angelman syndrome and Prader-Willi syndrome in CRISPR/Cas9-engineered human embryonic stem cells.

Angelman syndrome (AS) and Prader-Willi syndrome (PWS), two distinct neurodevelopmental disorders, result from loss of expression from imprinted genes in the chromosome 15q11-13 locus most commonly caused by a megabase-scale deletion on either the maternal or paternal allele, respectively. Each occurs at an approximate incidence of 1/15,000 to 1/30,000 live births and has a range of debilitating phenotypes. Patient-derived induced pluripotent stem cells (iPSCs) have been valuable tools to understand human-relevant gene regulation at this locus and have contributed to the development of therapeutic approaches for AS.

The brain-gut axis: communication mechanisms and the role of the microbiome as a neuroprotective factor in the development of neurodegenerative diseases: A literature overview.

The study of the brain-gut axis and its impact on cognitive function and in the development of neurodegenerative diseases is a very timely topic of interest to researchers. This review summarizes information on the basic mechanisms of gut-brain communication. We then discuss the roles of the gut microbiome as a neuroprotective factor in neurodegeneration.

[Evaluation of the regeneration process of the sciatic nerve of a mouse animal model after application of freezing, crushing or electrocoagulation damage].

The problem of regeneration of damaged peripheral nerves is an ongoing topic and has long been the subject of intensive research worldwide. This study examined the morphological and functional evaluation of the regeneration process within the damaged sciatic nerve, a mouse animal model. The effect of impaired expression of the TSC-1 gene on the process of nerve regeneration was evaluated, depending on the mode of damage.

[The mTOR pathway and transgenic animals with deletion of the TSC gene in the regeneration of the nervous system and selected models of sciatic nerve damage].

Traumatic damage to the nervous system has been a common occurrence for years, reducing patients' quality of life. The mammalian target of rapamycin (mTOR) pathway plays a key role in nervous system physiology, including by controlling nerve cell survival and differentiation. Excessive activation of the mTOR pathway leads to an increase in cell cycle protein activity and apoptosis of nerve cells.

[Assessment of metabolomics in patients with multiple sclerosis as an indicator of disease development, including relapsing-remitting, primary progressive and secondary progressive stage].

Metabolomics is a scientific field whose topics include qualitative and quantitative analysis of metabolites, defined as the total set of low-molecular-weight chemical compounds not exceeding 1500 Da. Along with genomics, transcriptomics, and proteomics, it is categorized as a field of science, currently using state-of-the-art diagnostic tools that, in the face of modern medicine, allow a holistic approach to the patient. The presence of metabolites in the analyzed biological material, in contrast to the information contained directly in the genetic material, reflects the current physiological state of the cell, and represents an integral relationship between genotype and phenotype, which can directly contribute in the future to the knowledge of the molecular basis in specific disease entities.

Generation of isogenic models of Angelman syndrome and Prader-Willi syndrome in CRISPR/Cas9-engineered human embryonic stem cells.

Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS), two distinct neurodevelopmental disorders, result from loss of expression from imprinted genes in the chromosome 15q11-13 locus most commonly caused by a megabase-scale deletion on either the maternal or paternal allele, respectively. Each occurs at an approximate incidence of 1/15,000 to 1/30,000 live births and has a range of debilitating phenotypes. Patient-derived induced pluripotent stem cells (iPSCs) have been valuable tools to understand human-relevant gene regulation at this locus and have contributed to the development of therapeutic approaches for AS.

[Neuroprotective effect of curcumin and its potential use in the treatment of neurodegenerative diseases].

The development of methods used in molecular biology has allowed a milestone in medical and pharmaceutical sciences. Progress has also been made in the field of pharmacognosy, which places substances of natural origin contained in plant raw materials at the center of attention. The beneficial effects of some of them have been known for years, while scientific evidence of their health-promoting properties was lacking for a long time.

The role of UBE3A in the autism and epilepsy-related Dup15q syndrome using patient-derived, CRISPR-corrected neurons.

Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurodevelopmental disorder caused by maternal duplications of this region. Autism and epilepsy are key features of Dup15q. UBE3A, which encodes an E3 ubiquitin ligase, is likely a major driver of Dup15q because UBE3A is the only imprinted gene expressed solely from the maternal allele.

[Cerebral metabolism of glucose and selected glucose transporters in neurodegenerative diseases].

Cerebral glucose metabolism is an issue of researchers’ interest for a long time. Disturbed transport and metabolism of glucose in the brain lead to development of numerous neurological pathologies. Recently, a significant correlation between perturbed cerebral glucose metabolism and development of neurodegenerative diseases has been shown.

Specific ZNF274 binding interference at SNORD116 activates the maternal transcripts in Prader-Willi syndrome neurons.

Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay and hyperphagia/obesity. This disorder is caused by the absence of paternally expressed gene products from chromosome 15q11-q13. We previously demonstrated that knocking out ZNF274, a Kruppel-associated box-A-domain zinc finger protein capable of recruiting epigenetic machinery to deposit the H3K9me3 repressive histone modification, can activate expression from the normally silent maternal allele of SNORD116 in neurons derived from PWS induced pluripotent stem cells (iPSCs).

Abundance and localization of human UBE3A protein isoforms.

Loss of UBE3A expression, a gene regulated by genomic imprinting, causes Angelman syndrome (AS), a rare neurodevelopmental disorder. The UBE3A gene encodes an E3 ubiquitin ligase with three known protein isoforms in humans. Studies in mouse suggest that the human isoforms may have differences in localization and neuronal function.

Chemical and Physical Transformations of Silver Nanomaterial Containing Textiles After Modeled Human Exposure.

The antimicrobial properties of silver nanomaterials (AgNM) have been exploited in various consumer applications, including textiles such as wound dressings. Understanding how these materials chemically transform throughout their use is necessary to predict their efficacy during use and their behavior after disposal. The aim of this work was to evaluate chemical and physical transformations to a commercial AgNM-containing wound dressing during modeled human exposure to synthetic sweat (SW) or simulated wound fluid (WF).

Dosing, Not the Dose: Comparing Chronic and Pulsed Silver Nanoparticle Exposures.

The environmental impacts of manufactured nanoparticles are often studied using high-concentration pulse-additions of freshly synthesized nanoparticles, while predicted releases are characterized by chronic low-concentration additions of weathered particles. To test the effects in wetlands of addition rate and nanoparticle speciation on water column silver concentrations, ecosystem impacts, and silver accumulation by biota, we conducted a year-long mesocosm experiment. We compared a pulse addition of Ag-NPs to chronic weekly additions of either Ag-NPs or sulfidized silver nanoparticles.

Oral Ingestion and Intraventricular Injection of Curcumin Attenuates the Effort-Related Effects of the VMAT-2 Inhibitor Tetrabenazine: Implications for Motivational Symptoms of Depression.

Effort-related choice tasks are used for studying depressive motivational symptoms such as anergia/fatigue. These studies investigated the ability of the dietary supplement curcumin to reverse the low-effort bias induced by the monoamine storage blocker tetrabenazine. Tetrabenazine shifted effort-related choice in rats, decreasing high-effort lever pressing but increasing chow intake.

Effect of Direct Contact on the Phytotoxicity of Silver Nanomaterials.

The increasing use of silver nanomaterials (AgNMs) in consumer products will result in an increased amount entering the environment, where AgNMs were recently found to cause phytotoxicity in the model plant Lolium multiflorum. To better understand the causes of the phytotoxicity, we have designed a new set of experiments to study the effect of AgNM dissolution. Dissolution of AgNMs was measured over a 1-month period to determine if dissolution alone caused phytotoxicity.

Phytotoxicity of soluble graphitic nanofibers to model plant species.

Carbon nanomaterials are considered promising for applications in energy storage, catalysis, and electronics. This has motivated study of their potential environmental toxicity. Recently, a novel nanomaterial consisting of graphene oxide wrapped around a carbon nanotube (CNT) core was synthesized.

Reducing Environmental Toxicity of Silver Nanoparticles through Shape Control.

The use of antibacterial silver nanomaterials in consumer products ranging from textiles to toys has given rise to concerns over their environmental toxicity. These materials, primarily nanoparticles, have been shown to be toxic to a wide range of organisms; thus methods and materials that reduce their environmental toxicity while retaining their useful antibacterial properties can potentially solve this problem. Here we demonstrate that silver nanocubes display a lower toxicity toward the model plant species Lolium multiflorum while showing similar toxicity toward other environmentally relevant and model organisms (Danio rerio and Caenorhabditis elegans) and bacterial species (Esherichia coli, Bacillus cereus, and Pseudomonas aeruginosa) compared to quasi-spherical silver nanoparticles and silver nanowires.

Refining the statistical model for quantitative immunostaining of surface-functionalized nanoparticles by AFM.

Recently, an atomic force microscopy (AFM)-based approach for quantifying the number of biological molecules conjugated to a nanoparticle surface at low number densities was reported. The number of target molecules conjugated to the analyte nanoparticle can be determined with single nanoparticle fidelity using antibody-mediated self-assembly to decorate the analyte nanoparticles with probe nanoparticles (i.e.

Concentrations and activities of metalloproteinases 2 and 9 and their inhibitors (TIMPS) in chronic pancreatitis and pancreatic adenocarcinoma.

Unlabelled: Pancreatic cancer (PC) and chronic pancreatitis (CP) are still significant problems. The aim of this study was a comparative analysis of the activity and concentrations of matrix metalloproteinases 2 and 9 and the concentrations of their tissue inhibitors (TIMP 1 and 2) in the PC compared to CP tissue homogenates. The study was performed in a group of 63 patients with pancreatic cancer or chronic pancreatitis selected for resection procedures.

The changes in neurotrophic properties of the peripheral nerves extracts following blocking of BDNF activity.

Objectives: Retinal ganglion cells (RGCs) of adult rats are unable to regenerate their axons after optic nerve injury and soon after they enter the pathway of apoptosis. They may, however, survive and regenerate new axons in response to application of specific peripheral nerve extracts that presumably contain a range of neurotrophic substances. One of the recognized substances of proven neurotrophic activity is brain-derived neurotrophic factor (BDNF).

Quantitative and qualitative analysis of proteins in rat peripheral nerves predegenerated for 7 days.

Objectives: In contrast to peripheral nerves, central neurons do not regrow spontaneously after injury. Our previous studies showed that transplantation of degenerating peripheral nerves or their extracts can induce regeneration in the injured central nervous system. Non-predegenerated nerves show much weaker neurotrophic activity.

[Neutrophins in biology and medicine].

Nerve growth factor NGF was the first neurotrophic substance to be identified, isolated, and characterized. NGF is member of a class of substances which has been termed the neurotrophins familly. This family of NGF-related trophic factors includes also brain-derived neurotrophic factor--BDNF, neurotrophin-3, neurotrophin-4/5 and neurotrophin-6 and 7.