Marking a Century of the Department of Chemistry and Biochemistry at School of Medicine in Zagreb: Honoring Professors Tomislav Pinter and Mihovil Proštenik as Fran Bubanović’s Successors

In 2018 the Department of Chemistry and Biochemistry at Zagreb School of Medicine celebrated 100 years since it was established by professor Fran Bubanović. This essay is focused on his successors, outstanding teachers and scientists, professors Tomislav Pinter and Mihovil Proštenik, members of Yugoslavian (today Croatian) Academy of Sciences and Arts. Tomislav Pinter was a prominent physical chemist who had an original approach and gave novel interpretation of van der Waals and Wohl’s equations. He also served as the president of Croatian Chemical Society. Neurobiochemist Mihovil Proštenik started as an organic chemist at “Prelog’s Zagreb School of Organic Chemistry”. He collaborated with two Croatian Nobel prize winners in chemistry: his PhD thesis supervisor Vladimir Prelog and Lavoslav Ružička. He was the founder of “Zagreb School of Lipidology”, discovered a new sphingoid base C20-sphingosine, and had a major role in the establishment of Ruđer Bošković Institute. Herein we honor their contributions to Croatian science and beyond, and share so far unpublished valuable material from the Department archive. This work is licensed under a Creative Commons Attribution 4.0 International License

Fran Bubanović: The Visionary of Medical Chemistry and Biochemistry in Croatia

Professor Fran Bubanović was the founder of the Department of Chemistry and Biochemistry at School of Medicine established a hundred years ago, in 1917, within the University of Zagreb. Fran Bubanović was an exemplary scientist, great science communicator and teacher. He trained many generations of physicians in chemistry and biochemistry. The aim of this essay is to give insight into his scientific collaboration with the Nobel Prize winner Svante Arrhenius and other world-renowned scientists, his teaching work in chemistry, his university textbooks in the field of medical chemistry and biochemistry since he had a profound impact on education of medical students in basic science. We hope that this essay will bring an additional dimension of Fran Bubanović as a superb university teacher and scientist whose legacy still remains unequalled. Therefore, he is legitimately called “the father of medical chemistry” in Croatia. This work is licensed under a Creative Commons Attribution 4.0 International License

Fran Bubanović: The Visionary of Medical Chemistry and Biochemistry in Croatia

Professor Fran Bubanović was the founder of the Department of Chemistry and Biochemistry at School of Medicine established a hundred years ago, in 1917, within the University of Zagreb. Fran Bubanović was an exemplary scientist, great science communicator and teacher. He trained many generations of physicians in chemistry and biochemistry. The aim of this essay is to give insight into his scientific collaboration with the Nobel Prize winner Svante Arrhenius and other world-renowned scientists, his teaching work in chemistry, his university textbooks in the field of medical chemistry and biochemistry since he had a profound impact on education of medical students in basic science. We hope that this essay will bring an additional dimension of Fran Bubanović as a superb university teacher and scientist whose legacy still remains unequalled. Therefore, he is legitimately called “the father of medical chemistry” in Croatia. This work is licensed under a Creative Commons Attribution 4.0 International License

History of Chemistry and Chemical Engineering: 135th Birth Anniversary of Fran Bubanović: Notes from His Life

U ovom radu prikazane su crtice iz života jednog od velikana hrvatskog prirodoslovlja, kemičara Frana Bubanovića. Ove 2018. godine obilježavamo 135 godina od njegova rođenja, 100 godina postojanja Zavoda za kemiju i biokemiju Medicinskog fakulteta Sveučilišta u Zagrebu, čiji je osnivač, te 100 godina od izdavanja njegove znanstveno-popularne knjige “Kemija živih bića”. Kroz godine napisan je velik broj tekstova o njegovom doprinosu popularizaciji znanosti, znanstvenom opusu, njegovom nastavničkom pozivu kao i sveučilišnim udžbenicima. Ovim tekstom želimo se osvrnuti na pojedine zanimljive trenutke njegova života te prikazati nekoliko dosad neobjavljenih dokumenata i fotografija ustupljenih od njegove obitelji. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna.This paper gives an account of some details in the life of one of the most remarkable people in Croatian natural sciences, chemist Fran Bubanović. In 2018, we commemorate his 135th birth anniversary, 100th anniversary of the Department of Chemistry and Biochemistry founded by Bubanović at the School of Medicine, University of Zagreb, and a 100 years since the publishing of his popular science book “The Chemistry of Living Beings”. Throughout the years, numerous texts have been written regarding his contribution to science popularization, scientific work, his teaching career, as well as his university textbooks. In this text, we attempt to reflect on some specific moments in his life, as well as present several unpublished documents and photographs donated by his family. This work is licensed under a Creative Commons Attribution 4.0 International License

Povezica narušenog periodontalnog zdravlja u mlađih bolesnika sa shizofrenijom s pogoršanjem simptoma tijekom remisije: prospektivno kohortno istraživanje

Objectives - The aim of this prospective cohort study was to investigate whether the association of periodontal status with schizophrenia treatment outcomes differs by patient’s age. Subjects and methods - The study was performed on the consecutive sample of 67 patients diagnosed with schizophrenia and discharged because achieving remission criteria. Papilla bleeding index (PBI) was measured at hospital discharge. Positive and negative syndrome scale (PANSS) total score, positive, negative and general symptoms subscales’ scores were measured at hospital discharge, after three, and after six months. Results: - After the adjustment for potential confounders, baseline PBI was significantly unfavorably associated with PANSS total score, negative and general symptoms subscales scores in the patients younger than 45 three and six months after the hospital discharge, and with the positive symptoms sub-scale in patients younger than 34. At youngest 10% of patients, a unit difference in baseline PBI resulted in the 8.12 (95% CI 2.78-13.47; p=0.004) points higher total PANSS score three months later. Our study showed that the younger patients with worse periodontal status are at higher risk for poorer schizophrenia treatment outcomes and faster worsening of remission. This study demonstrates the necessity of more rigorous and more frequent control of younger schizophrenia patients with worse periodontal status after hospital discharge to achieve overall improvement of the patients’ quality of life as well as the efficacy of psychiatric therapies aimed toward the primary mental disorder.Cilj ove prospektivne kohortne studije bio je istražiti postoji li razlika u povezanosti parodontnog statusa sa slabljenjem kvalitete remisije shizofrenije ovisno o dobi pacijenta. Ispitanici i metode: - Istraživanje je provedeno na susljednom uzorku od 67 pacijenata s dijagnosticiranom shizofrenijom koji su otpušteni iz bolnice radi ostvarenih kriterija remisije. Indeks krvareće papile (PBI, engl. papilla bleeding index) izmjeren je pri otpustu iz bolnice. Ispitanici su procijenjeni ljestvicom pozitivnih i negativnih simptoma (PANSS) pri otpustu iz bolnice, nakon tri i nakon šest mjeseci. Rezultati: - Nakon prilagodbe za potencijalne zbunjujuće varijable, indeks krvareće papile bio je značajno inverzno povezan s ukupnim PANSS rezultatom, te rezultatom subljestvica za negativne i generalne psihotične simptome kod pacijenata mlađih od 45 godina nakon tri i nakon šest mjeseci poslije otpusta iz bolnice, te s rezultatom subljestvice za pozitivne simptome kod pacijenata mlađih od 34 godine. Kod najmlađih 10% pacijenata, jedinična razlika u indeksu krvareće papile bila je za 8.12 (95% CI 2.78-13.47; p=0.004) viša za ukupni PANSS rezultat tri mjeseca nakon otpusta iz bolnice. Zaključci: Naše je istraživanje pokazalo da mlađi pacijenti s lošijim parodontnim statusom imaju povećan rizik za lošiju kvalitetu remisije shizofrenije, odnosno brže pogoršanje simptoma tijekom remisije. Ovo istraživanje ukazuje na potrebu za pojačanom i češćom kontrolom mlađih pacijenata sa shizofrenijom koji imaju lošiji parodontni status nakon otpusta iz bolnice kako bi poboljšali kvalitetu života pacijenta kao i pridonijeli učinkovitijoj terapiji primarnog mentalnog poremećaja

Hippocampal expression of cell-adhesion glycoprotein neuroplastin is altered in Alzheimer's disease

Cell-adhesion glycoprotein neuroplastin (Np) is involved in the regulation of synaptic plasticity and balancing hippocampal excitatory/inhibitory inputs which aids in the process of associative memory formation and learning. Our recent findings show that neuroplastin expression in the adult human hippocampus is specifically associated with major hippocampal excitatory pathways and is related to neuronal calcium regulation. Here, we investigated the hippocampal expression of brain-specific neuroplastin isoform (Np65), its relationship with amyloid and tau pathology in Alzheimer's disease (AD), and potential involvement of neuroplastin in tissue response during the disease progression. Np65 expression and localization was analysed in six human hippocampi with confirmed AD neuropathology, and six age-/gender-matched control hippocampi by imunohistochemistry. In AD cases with shorter disease duration, the Np65 immunoreactivity was significantly increased in the dentate gyrus (DG), Cornu Ammonis 2/3 (CA2/3), and subiculum, with the highest level of Np expression being located on the dendrites of granule cells and subicular pyramidal neurons. Changes in the expression of neuroplastin in AD hippocampal areas seem to be related to the progression of disease. Our study suggests that cell-adhesion protein neuroplastin is involved in tissue reorganization and is a potential molecular marker of plasticity response in the early neurodegeneration process of AD

Plasma Membrane Calcium ATPase-Neuroplastin Complexes Are Selectively Stabilized in GM1-Containing Lipid Rafts

The recent identification of plasma membrane (Ca2+)-ATPase (PMCA)-Neuroplastin (Np) complexes has renewed attention on cell regulation of cytosolic calcium extrusion, which is of particular relevance in neurons. Here, we tested the hypothesis that PMCA-Neuroplastin complexes exist in specific ganglioside-containing rafts, which could affect calcium homeostasis. We analyzed the abundance of all four PMCA paralogs (PMCA1-4) and Neuroplastin isoforms (Np65 and Np55) in lipid rafts and bulk membrane fractions from GM2/GD2 synthase-deficient mouse brains. In these fractions, we found altered distribution of Np65/Np55 and selected PMCA isoforms, namely PMCA1 and 2. Cell surface staining and confocal microscopy identified GM1 as the main complex ganglioside co-localizing with Neuroplastin in cultured hippocampal neurons. Furthermore, blocking GM1 with a specific antibody resulted in delayed calcium restoration of electrically evoked calcium transients in the soma of hippocampal neurons. The content and composition of all ganglioside species were unchanged in Neuroplastin-deficient mouse brains. Therefore, we conclude that altered composition or disorganization of ganglioside-containing rafts results in changed regulation of calcium signals in neurons. We propose that GM1 could be a key sphingolipid for ensuring proper location of the PMCA-Neuroplastin complexes into rafts in order to participate in the regulation of neuronal calcium homeostasis

Nastava kemije i biokemije na Medicinskom fakultetu u Zagrebu u doba Frana Bubanovića [Chemistry and biochemistry education at School of medicine in Zagreb at the time of Fran Bubanović]

Exactly a hundred years ago the Department of Chemistry and Biochemistry was established within the newly founded School of Medicine in Zagreb. Its founder, first Department Head and Professor was Fran Bubanović. Education of future physicians in medical chemistry and biochemistry is continuously performed since 1918. This paper aims to provide an insight in teaching activities at the Department throughout almost forty years of Bubanović’s university career. The contribution of professor Bubanović is unmeasurable not only in the early years of the Department teaching activity, but also to the organisation and management of courses and the Department throughout many years, as well as to university literature in chemistry. We believe that professor Bubanović has made a profound impact on many generations of students with his dedicated work, and us, his successors, he left forever indebted

Start Me Up: How Can Surrounding Gangliosides Affect Sodium-Potassium ATPase Activity and Steer towards Pathological Ion Imbalance in Neurons?

Gangliosides, amphiphilic glycosphingolipids, tend to associate laterally with other membrane constituents and undergo extensive interactions with membrane proteins in cis or trans configurations. Studies of human diseases resulting from mutations in the ganglioside biosynthesis pathway and research on transgenic mice with the same mutations implicate gangliosides in the pathogenesis of epilepsy. Gangliosides are reported to affect the activity of the Na+/K+-ATPase, the ubiquitously expressed plasma membrane pump responsible for the stabilization of the resting membrane potential by hyperpolarization, firing up the action potential and ion homeostasis. Impaired Na+/K+-ATPase activity has also been hypothesized to cause seizures by several mechanisms. In this review we present different epileptic phenotypes that are caused by impaired activity of Na+/K+-ATPase or changed membrane ganglioside composition. We further discuss how gangliosides may influence Na+/K+-ATPase activity by acting as lipid sorting machinery providing the optimal stage for Na+/K+-ATPase function. By establishing a distinct lipid environment, together with other membrane lipids, gangliosides possibly modulate Na+/K+-ATPase activity and aid in “starting up” and “turning off” this vital pump. Therefore, structural changes of neuronal membranes caused by altered ganglioside composition can be a contributing factor leading to aberrant Na+/K+-ATPase activity and ion imbalance priming neurons for pathological firing

Neuroplastin in human cognition: review of literature and future perspectives

Synaptic glycoprotein neuroplastin is involved in synaptic plasticity and complex molecular events underlying learning and memory. Studies in mice and rats suggest that neuroplastin is essential for cognition, as it is needed for long-term potentiation and associative memory formation. Recently, it was found that some of the effects of neuroplastin are related to regulation of calcium homeostasis through interactions with plasma membrane calcium ATPases. Neuroplastin is increasingly seen as a key factor in complex brain functions, but studies in humans remain scarce. Here we summarize present knowledge about neuroplastin in human tissues and argue its genetic association with cortical thickness, intelligence, schizophrenia, and autism; specific immunolocalization depicting hippocampal trisynaptic pathway; potential role in tissue compensatory response in neurodegeneration; and high, almost housekeeping, level of spatio-temporal gene expression in the human brain. We also propose that neuroplastin acts as a housekeeper of neuroplasticity, and that it may be considered as an important novel cognition-related molecule in humans. Several promising directions for future investigations are suggested, which may complete our understanding of neuroplastin actions in molecular basis of human cognition