Age-dependent oxidative stress: toward an irreversible failure in endothelial maintenance

In order to maintain cellular homeostasis against endogenous and exogenous aggressions, different cellular mechanisms of defence, maintenance and repair are continuously activated throughout life. Hormesis, a concept based on the fact that mild stresses protect cells against subsequent stresses, amplifies the efficacy of the cellular mechanisms of defence and repair. Ageing, senescence and ultimately death, result from the exhaustion of these mechanisms maintaining cellular functions. One of the major sources of vascular endothelial damage is oxidative stress. The age-dependent shift in the redox environment towards pro-oxidation contributes to a progressive compensatory remodelling of the endothelium, an accumulation of damages, and its dysfunction, the premises for atherosclerosis. We propose that in agreement with the concept of hormesis, a moderate exposure during endothelial maturation to mild physiological oxidative stressors determines -vascular longevity.     

Characterization of a novel MK3 splice variant from murine ventricular myocardium

p38 MAP kinase (MAPK) isoforms α, β, and γ, are expressed in the heart. p38α appears pro-apoptotic whereas p38β is pro-hypertrophic. The mechanisms mediating these divergent effects are unknown; hence elucidating the downstream signaling of p38 should further our understanding. Downstream effectors include MAPK-activated protein kinase (MK)-3, which is expressed in many tissues including skeletal muscles and heart. We cloned full-length MK3 (MK3.1, 384 aa) and a novel splice variant (MK3.2, 266 aa) from murine heart. For MK3.2, skipping of exons 8 and 9 resulted in a frame-shift in translation of the first 85 base pairs of exon 10 followed by an in-frame stop codon. Of 3 putative phosphorylation sites for p38 MAPK, only Thr-203 remained functional in MK3.2. In addition, MK3.2 lacked nuclear localization and export signals. Quantitative real-time PCR confirmed the presence of these mRNA species in heart and skeletal muscle; however, the relative abundance of MK3.2 differed. Furthermore, whereas total MK3 mRNA was increased, the relative abundance of MK3.2 mRNA decreased in MK2^?/? mice. Immunoblotting revealed 2 bands of MK3 immunoreactivity in ventricular lysates. Ectopically expressed MK3.1 localized to the nucleus whereas MK3.2 was distributed throughout the cell; however, whereas MK3.1 translocated to the cytoplasm in response to osmotic stress, MK3.2 was degraded. The p38α/β inhibitor SB203580 prevented the degradation of MK3.2. Furthermore, replacing Thr-203 with alanine prevented the loss of MK3.2 following osmotic stress, as did pretreatment with the proteosome inhibitor MG132. In vitro, GST-MK3.1 was strongly phosphorylated by p38α and p38β, but a poor substrate for p38δ and p38γ. GST-MK3.2 was poorly phosphorylated by p38α and p38β and not phosphorylated by p38δ and p38γ. Hence, differential regulation of MKs may, in part, explain diverse downstream effects mediated by p38 signaling.     

Pediatric idiopathic intracranial hypertension: clinical and demographic features

Idiopathic intracranial hypertension (IIH) is a clinical condition characterized by elevated intracranial pressure and absence of clinical, laboratory or radiographic evidence of central nervous system infection, vascular malformation, intracranial space occupying lesion or hydrocephalus. In the last years the raising understanding of pediatric IIH, especially concerning its demographics and epidemiology, has brought up to a redefinition of diagnostic criteria and reevaluation of pathogenesis and treatment. The authors reviewed the records of nineteen consecutive children with newly diagnosed IIH in order to compare demographic characteristics, clinical pictures and ophthalmologic aspects as optic disc evaluation and visual field evaluation, as well as treatment modalities and follow up. Beside obesity and female gender, potential alternative risk factors remains to be investigated, which need a good collaboration between neuro-ophthalmologists and pediatric neurologists.     

Postinfectious glomerulonephritis and Epstein-barr virus co-infection

Contrary to group A beta-hemolytic streptococcus as the most common cause of postinfectious glomerulonephritis (PIGN), Epstein-Barr virus (EBV) is only occasionally associated with acute renal involvement. We describe an 11-year-old boy who presented with clinical signs of infective mononucleosis and acute glomerulonephritis characterized by edema, hypertension and dark colored urine with diminished renal function. Serology tests confirmed streptococcal infection and acute EBV infection. Persistently depressed C3 complement and gross hematuria indicated renal biopsy which shows PIGN-type picture and, in addition, acute interstitial nephritis, both conclusive of streptococcal infection. We performed tissue DNA extraction by polymerase chain reaction (PCR) and demonstrated EBV-DNA from the kidney specimen supporting EBV involvement in renal tissue. This is the first reported case of PIGN with serologically-proven streptococcal and simultaneously, acute EBV co-infection. EBV-DNA extraction supported the EBV involvement in renal tissue suggesting that both etiologic agents might have contributed to renal inflammation. Adding serology evaluation for EBV in cases with typical clinical signs of infective mononucleosis and renal symptoms, EBV might be more commonly associated with PIGN than is currently appreciated.     

The role of air quality in perception of health of the local population

The research aim was to investigate and establish the perception of health among population groups with different number of industrial polluters in their living environment. Namely, the Kostrena living area (3250 inhabitants) is situated near big industrial pollutant producers: INA oil refinery Urinj, thermo power plant Rijeka, shipyard "Viktor Lenac", while in Crikvenica living area such pollutant producers do not exist. In this research 146 subjects from Kostrena participated (74 men and 72 women with age average 40.8, SD 9.2 years), and 157 subjects from Crikvenica area (79 men and 78 women with age average 39.4, SD 10.1 years). The perception of health was measured by the means of SF-36 questionnaire variables. Lung function (FEV1, FVC, FEV25/75, PEF), cardiovascular function (systolic and diastolic arterial blood pressure, heart rate were also measured, including body proportion measures by the means of waste and hip circumference and silhouette test, in order to establish the eventual objective physical health parameter difference among examined population groups. Subjects from Kostrena perceived their general health, mental health, and vitality worse than subjects from Crikvenica. Group from Kostrena felt themself more limited in their roles due to emotional problems, perceiving more pain than group from Crikvenica. On the opposite site, social functioning of subjects from Kostrena was better in comparison to Crikvenica group. No signifficant differences between groups were found in physical functioning and in role limitation due to physical problems. In addition, there were no significant differences between groups in objective physical health parameters, such as pulmonary function, arterial blood pressure, pulse, and waist to hip ratio. Subjects using sensoric systems and the mental cognition about harmful environmental factors, perceive their health worse if there are present industrial resources in their environment, even when concentration of the pollutants are within legal ranges.     

QEEG characteristics and spectrum weighted frequency for children diagnosed as autistic spectrum disorder

Background

Autistic spectrum disorders are a group of neurological and developmental disorders associated with social, communication, sensory, behavioral and cognitive impairments, as well as restricted, repetitive patterns of behavior, activities, or interests.The aim of this study was a) to analyze QEEG findings of autistic patients and to compare the results with data base; and b) to introduce the calculation of spectrum weighted frequency (brain rate) as an indicator of general mental arousal in these patients.

Results

Results for Q-EEG shows generally increased delta-theta activity in frontal region of the brain. Changes in QEEG pattern appeared to be in a non-linear correlation with maturational processes.Brain rate measured in CZ shows slow brain activity (5. 86) which is significantly lower than normal and corresponds to low general mental arousal.Recent research has shown that autistic disorders have as their basis disturbances of neural connectivity. Neurofeedback seems capable of remediating such disturbances when these data are considered as part of treatment planning.

Conclusions

Prognosis of this pervasive disorder depends on the intellectual abilities: the better intellectual functioning, the possibilities for life adaptation are higherQEEG shows generally increased delta-theta activity in frontal region of the brain which is related to poor cognitive abilities.Brain rate measured in CZ shows slow brain activity related to under arousal.Pharmacotherapy combined with behavior therapy, social support and especially neurofeedback technique promise slight improvements

     

Preparation of novel authentication film by screen printing of anthocyanin biomolecular extract: Thermochromism and vapochromism

Novel thermochromic and vapochromic paper substrates were prepared via screen printing with anthocyanin extract in the presence of ferrous sulfate mordant, resulting in multi-stimuli responsive colorimetric paper sheets. Environmentally friendly anthocyanin extract was obtained from red-cabbage (Brassica oleracea var. capitata L.) to function as spectroscopic probe in coordination with ferrous sulfate mordant. Pink anthocyanin/resin nanocomposite films immobilized onto paper surface were developed by well-dispersion of anthocyanin extract as a colorimetric probe in a binding agent without agglomeration. As demonstrated by CIE colorimetric studies, the pink (λ_max = 418 nm) film deposited onto paper surface turns greenish-yellow (λ_max = 552 nm) upon heating from 25 to 75°C, demonstrating new thermochromic film for anti-counterfeiting applications. The thermochromic effects were investigated at different concentrations of the anthocyanin extract. Upon exposure to ammonia gas, the color of the anthocyanin-printed sheets changes rapidly from pink to greenish-yellow, and then immediately returns to pink after taking the gaseous ammonia stimulus away, demonstrating vapochromic effect. The current sensor strip showed a detection limit for ammonia gas in the range 50–300 ppm. Both thermochromism and vapochromism showed high reversibility without fatigue. In addition to studying the rheological properties of the prepared composites, the morphological and mechanical properties of the printed cellulose substrates were also studied.     

Severity of the Omicron SARS-CoV-2 variant compared with the previous lineages: A systematic review

The Omicron variant was first detected in October 2021, which evolved from the original SARS-CoV-2 strain and was found to possess many mutations. Immune evasion was one of the notable consequences of these mutations. Despite Omicron exhibiting increased transmissibility, the rates of hospitalizations and deaths among patients infected with this variant were substantially lower when compared to other strains. However, concluding that the Omicron variant is less severe than other variants of SARS-CoV-2 requires consideration of multiple factors, including the vaccination status of infected patients as well as any previous infections with other variants. This review compiled data about any reported indicators of severity in Omicron-infected patients, including studies comparing Omicron with other variants while adjusting for confounders. A comprehensive search was conducted using different databases to target any studies about Omicron. In total, 62 studies met our inclusion criteria and were included in this study. Many studies reported a significantly reduced risk of hospitalization, ICU admission, need for oxygenation/ventilation, and death in Omicron-infected patients compared to patients infected with other variants, such as Delta. Some studies, however, reported comparable severity in Omicron infected patients as to other variants emphasizing a substantial risk for severe illness. Furthermore, the COVID-19 vaccines were less effective against Omicron relative to previous lineages, except after receiving the booster dose. One study recommended vaccination during pregnancy, which may help prevent future cases of severe SARS-CoV-2 pneumonia in neonates and young infants due to the transfer of humoral response from the mother.     

H-Ras, R-Ras, and TC21 differentially regulate ureteric bud cell branching morphogenesis

The collecting system of the kidney, derived from the ureteric bud (UB), undergoes repetitive bifid branching events during early development followed by a phase of tubular growth and elongation. Although members of the Ras GTPase family control cell growth, differentiation, proliferation, and migration, their role in development of the collecting system of the kidney is unexplored. In this study, we demonstrate that members of the R-Ras family of proteins, R-Ras and TC21, are expressed in the murine collecting system at E13.5, whereas H-Ras is only detected at day E17.5. Using murine UB cells expressing activated H-Ras, R-Ras, and TC21, we demonstrate that R-Ras-expressing cells show increased branching morphogenesis and cell growth, TC21-expressing cells branch excessively but lose their ability to migrate, whereas H-Ras-expressing cells migrated the most and formed long unbranched tubules. These differences in branching morphogenesis are mediated by differential regulation/activation of the Rho family of GTPases and mitogen-activated protein kinases. Because most branching of the UB occurs early in development, it is conceivable that R-Ras and TC-21 play a role in facilitating branching and growth in early UB development, whereas H-Ras might favor cell migration and elongation of tubules, events that occur later in development.     

Membrane deformation under local pH gradient: mimicking mitochondrial cristae dynamics

Mitochondria are cell substructures (organelles) critical for cell life, because biological fuel production, the ATP synthesis by oxidative phosphorylation, occurs in them driven by acidity (pH) gradients. Mitochondria play a key role as well in the cell death and in various fatigue and exercise intolerance syndromes. It is clear now that mitochondria present an astonishing variety of inner membrane morphologies, dynamically correlated with their functional state, coupled with the rate of the ATP synthesis, and characteristic for normal as well as for pathological cases. Our work offers some original insights into the factors that determine the dynamical tubular structures of the inner membrane cristae. We show the possibility to induce, by localized proton flow, a macroscopic cristae-like shape remodeling of an only-lipid membrane. We designed a minimal membrane system (GUV) and experimentally showed that the directional modulation of local pH gradient at membrane level of cardiolipin-containing vesicles induces dynamic cristae-like membrane invaginations. We propose a mechanism and theoretical model to explain the observed tubular membrane morphology and suggest the underlying role of cardiolipin. Our results support the hypothesis of localized bioenergetic transduction and contribute to showing the inherent capacity of cristae morphology to become self-maintaining and to optimize the ATP synthesis.