The very definition, scope, and practical implications of the concept of vulnerability are among the most debated questions in the field of vulnerability research. However, a consensus seems to exist ...regarding children and adolescents: they are generally considered vulnerable and in need of special protection due to their physical and psychological immaturity, lack of knowledge and life experience, and overall dependency on adults. The special status of this population is safeguarded in numerous legal and ethics documents. In this paper, we discuss the commercial use of transcranial direct current stimulation (tDCS), as a method that have potential to affect functioning of the brain tissue with electrical currents, but also a variety of digital methods used to influence the brain. tDCS is openly advertised, affordable and accessible, even to minors. However, changes that tDCS and similar methods could induce in developing brain tissue and consequently their interference with the normal neurodevelopmental processes could have far-reaching health ramifications and thus represent new sources of vulnerability that slip under the radar of formalized legal and ethics documents. This article discusses changes in the adolescent brain during development and address whether adolescents who would wish to use these neuroenhancement procedures should be considered vulnerable and on what grounds.
Sama definicija, opseg i praktične implikacije koncepta ranjivosti su među najčešće raspravljanim pitanjima u području istraživanja ranjivosti. Zbog njihove fizičke i psihološke nezrelosti, nedostatka znanja i životnog iskustva te sveukupne ovisnosti o odraslima, postoji konsenzus da se djeca i adolescenti općenito smatraju ranjivima, te da ih je potrebno zaštititi. Poseban status ove populacije potvrđen je i u brojnim zakonskim i etičkim dokumentima. U radu raspravljamo o komercijalnoj upotrebi transkranijalne stimulacije istosmjernom strujom (tDCS) kao metode koja, djelujući s električnom strujom, može utjecati na funkcioniranje moždanog tkiva. Također govorimo i o ostalim digitalnim metodama koje se koriste za djelovanje na mozak. tDSC se otvoreno oglašava, pristupačan je cijenom i dostupan, čak i maloljetnicima. No, promjene koje bi tDCS i slične metode mogle potaknuti u razvoju moždanog tkiva i posljedično njihovu interferenciju s normalnim neurorazvojnim procesima mogle bi imati dalekosežne zdravstvene posljedice i tako predstavljati nove izvore ranjivosti koji nisu obuhvaćeni u formalnim pravnim i etičkim dokumentima. U ovom se članku raspravlja o promjenama u adolescentskom mozgu tijekom razvoja i pitanjem trebaju li se adolescenti koji žele koristiti ove postupke za neuropoboljšanje smatrati ranjivima i na temelju čega.
Oxidative stress is implicated in neuronal death in a variety of neurodegenerative diseases. In the present study, P19 neurons obtained by the differentiation procedure from mouse teratocarcinoma P19 ...cells were used to investigate the ability of quercetin, a plant-derived flavonoid, to prevent neuronal death induced by exposure to 150 μM or 1.5 mM hydrogen peroxide (H
2
O
2
) for 24 h. Quercetin treatment improved viability of P19 neurons exposed to both types of oxidative injury. During the modest oxidative stress, quercetin diminished generation of reactive oxygen species (ROS) and prevented H
2
O
2
-induced nuclear condensation, increase in caspase 3/7 activity and rise in poly(APD-ribose) polymerase expression. Expression of Bcl-2 family members Bax and Bcl-2 was not affected by quercetin treatment at both the transcriptional and translational levels. During the severe oxidative injury, quercetin prevented H
2
O
2
-induced rise in ROS accumulation and changes in plasma membrane integrity and nuclear morphology. The obtained results suggest that neuroprotective effects of quercetin are related to its antioxidative action and prevention of events associated with programmed cell death cascade. In the light of these findings, one might assume beneficial effects of quercetin for the prevention of oxidative stress-driven neuronal loss in human aging and age-related neurodegenerative diseases.
U potrazi za savršenstvom u sportu, uz pomoć znanosti o sportu i pratećih tehnologija, ljudi pomiču granice svojih tjelesnih sposobnosti. Međutim, granice ljudskog uma još nisu u potpunosti ...istražene. Iako većina sportova ima snažnu komponentu tjelesne snage i vještine, oni su čvrsto isprepleteni s percepcijom i kognitivnim procesima. Savršena izvedba zahtijeva »savršeni mozak« i u potrazi za izvrsnošću sportaši posežu za različitim načinima neuropoboljšavanja. Neki od korištenih metoda poboljšanja podliježu dopinškoj kontroli, no neki od njih su (još uvijek) izvan regulatornih granica. Integriranjem neuroznanstvenih znanja s etičkom i društvenom misli, članak će analizirati različite primjere neuropoboljšavanja i povezane etičke probleme.
The association of immunoglobulin G (IgG) glycosylation changes with various human diseases and physiological conditions is well established. Since the mechanistical explanation of the regulation of ...IgG glycosylation and its functional role in these various states is still missing, the eyes of the biomedical community are now turned towards animal models, which enable intervention studies necessary for conclusions on causality. Mice are recognized and used as a good experimental model for human IgG glycosylation. However, smaller blood volumes, low IgG concentrations at young ages (which are most often used in mice experiments) and multiple sampling protocols during the course of longitudinal studies would profit from a robust workflow for mouse IgG glycome analysis from minute amounts of starting material, collected through a simple sampling procedure. For this purpose, we have developed a protocol for analysis of total N‐glycans of IgG isolated from mouse dried blood spots (DBS), which we report here. We show that mouse DBS are a good source of material for IgG N‐glycan analysis by multiplexed capillary gel electrophoresis with laser‐induced fluorescence (xCGE‐LIF).
Immunoglobulin G (IgG) N-glycosylation is crucial for its effector functions. It is a complex trait, and large sample sets are needed to discover multiple genetic factors that underlie it. While in ...humans such high-throughput studies of IgG N-glycans became usual, only one has been carried out in mice. Here we describe and validate a method for the relative quantification of IgG Fc-linked N-glycans in a subclass-specific manner using nano-reverse phase liquid chromatography coupled with mass-spectrometry (nanoRP-LC-MS) applied to murine IgG. High-throughput data processing is ensured by the LaCyTools software. We have shown that IgG isolation procedure is the main source of technical variation in the current protocol. The major glycoforms were quantified reliably with coefficients of variation below 6% for all the analytes with relative abundances above 5%. We have applied our method to a sample set of 3 inbred strains: BALB/c, C57BL/6 and C3H and observed differences in subclass-specific and strain-specific N-glycosylation of IgG, suggesting a significant genetic component in the regulation of Fc-linked IgG N-glycosylation.
Copper, a transition metal with essential biological functions, exerts neurotoxic effects when present in excess. The aim of the present study was to better elucidate cellular and molecular ...mechanisms of CuSO
4
toxicity in differentiated P19 neurons. Exposure to 0.5 mM CuSO
4
for 24 h provoked moderate decrease in viability, accompanied with barely increased generation of reactive oxygen species (ROS) and caspase-3/7 activity. Glutathione (GSH) and ATP contents were depleted, lactate dehydrogenase inactivated, and glyceraldehyde-3-phosphate dehydrogenase overexpressed. In severely damaged neurons exposed to only two times higher concentration, classical caspase-dependent apoptosis was triggered as evidenced by marked caspase-3/7 activation and chromatin condensation. Multifold increase in ROS, together with very pronounced ATP and GSH loss, strongly suggests impairment of redox homeostasis. At higher copper concentration protease calpains were also activated, and neuronal injury was prevented in the presence of calpain inhibitor leupeptin through the mechanism that affects caspase activation. MK-801 and nifedipine, inhibitors of calcium entry, and H-89 and UO126, inhibitors of PKA and ERK signaling respectively, exacerbated neuronal death only in severely damaged neurons, while ROS-scavenger quercetin and calcium chelator BAPTA attenuated toxicity only at lower concentration. In a dose-dependent manner copper also provoked transcriptional changes of genes involved in intracellular signaling and induction of apoptosis (p53, c-fos, Bcl-2 and Bax). The obtained results emphasize differences in triggered neuronal-death processes in a very narrow range of concentrations and give further insight into the molecular mechanisms of copper toxicity with the potential to improve current therapeutic approaches in curing copper-related neurodegenerative diseases.
Projekt ljudskoga genoma završen je 2003. godine, a njegovi su rezultati otkrili dotada nepoznate detalje o našem genomu: skupinu informacija o tome kako ljudska bića izgledaju, kako djeluju, ...osjećaju, misle i razvijaju se. Uskoro su ostvarene i druge međunarodne suradnje poput projekta HapMap i Projekta 1000 genoma. Unatoč tomu što su primarno bili usmjereni na istraživanje varijabilnosti u ljudskoj populaciji, kao i moguće povezanosti različitih varijacija s različitim stanjima i bolestima, ti su projekti također znatno utjecali na razumijevanje utjecaja gena na sportski uspjeh. Usporedno su razvijene poboljšane metode genske analize i genskoga preinačavanja na temelju kojih je postalo moguće utvrditi kandidatske gene odgovorne za različite fenotipe uspješnosti u sportu te razviti protokole slične genskim terapijama za poboljšanje sportskih natjecateljskih performansi sportaša. Ovaj rad daje pregled razvoja u genetici, pregled kandidatskih gena povezanih sa sportskim natjecateljskim performansama te etičke dvojbe vezane uz preinačavanje genoma radi poboljšavanja sportskih natjecateljskih performansi.
Despite the excellent chemotherapeutic effect of irinotecan, its cytotoxicity and genotoxicity in normal cells remains a major problem in chemotherapy. This study was carried out to find whether ...propolis preparations and related flavonoids (quercetin, naringin) might enhance irinotecan-induced cytotoxicity to tumor cells in mice bearing Ehrlich ascites tumors (EAT) while protecting normal blood, liver, and kidney cells. The preparation of propolis and their flavonoids were given to mice intraperitoneally at a dose of 100 mg kg
−1
body weight for three consecutive days before the
ip
injection of EAT cells (2 × 10
6
). Irinotecan was administered
ip
at dose of 50 mg kg
−1
on days 3, 4, and 5 after tumor cell inoculation. The combination treatment resulted in substantial inhibition of the growth of EAT cells as well as treatment with quercetin or irinotecan alone, whereas other treatment by itself showed little effect. However, when mice were pre-treated with test components prior to irinotecan, the frequencies of irinotecan-induced micronuclei (MN) was decreased but in mice bearing tumor QU and EEP increased number of micronucleated cells. Propolis preparation and related flavonoids were found to exhibit an important immunomodulatory effect and could decrease irinotecan-induced toxic and genotoxic effects to normal cells without effecting irinotecan cytotoxicity in EAT cells.
Neurosteroid dehydroepiandrosterone sulfate (DHEAS) has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various ...neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration.
DHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-D-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on (3)Hflunitrazepam binding to the mouse brain membranes.
DHEAS did not modify the locomotor activity, motor coordination, body weight, and brain (3)Hflunitrazepam binding of male and female mice. The results failed to demonstrate significant effects of single- and long-term DHEAS treatment on the convulsive susceptibility in both adult and aged mice of both sexes. However, small but significant changes regarding sex differences in the susceptibility to seizures were observed following DHEAS administration to mice.
Although our findings suggest that DHEAS treatment might be safe for various potential therapeutic applications in adult as well as in old age, they also support subtle interaction of DHEAS with male and female hormonal status, which may underline observed sex differences in the relationship between DHEAS and various health outcomes.
PDF
