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DEVELOPMENT OF AN ELECTROCHEMICAL METHOD FOR MONITORING POLYSULFIDES (Sx2-) IN MARINE EUXINIC ENVIRONMENT
No full textDirektno analitičko određivanje polisulfida (Sx2-) u vodenim otopinama predstavlja izazov zbog niskih konstanti termodinamičke stabilnosti Sx2-. S ciljem razvoja i primjene direktne metode za određivanje i karakterizaciju Sx2-, istraživano je njihovo elektrokemijsko ponašanje na živinoj (Hg) elektrodi. Morski euksinski okoliš Rogozničkoga jezera – Zmajeva oka (RJ) izabran je kao model za ispitivanje elektroanalitičke metode (EM), difercijalno pulsne voltametrije (DPV) za direktno određivanje polisulfida u prirodnim uvjetima. Za praćenje reduciranih sumpornih specija (RSS), odnosno Sx2- uz DPV, korištene su i ciklička voltametrija (CV) i stepenasta DC voltametrija/polarografija (SDC), ali i druge analitičke metode: UV/Vis spektrofotometrija za dodatno određivanje Sx2-, te mikroskopija atomskih sila (eng. atomic forced microscopy, AFM) i dinamičko raspršenje svjetlosti (eng. dynamic light scattering, DLS) za praćenje promjene svojstava RSS. AFM-om je praćena promjena morfologije stanica fototrofnih sumpornih bakterija kao izvora elementarnog S pri različitim okolišnim i eksperimentalnim uvjetima, dok je s DLS praćena promjena hidrodinamičkog radijusa elementarnog S u različitim uvjetima razrjeđenja. DPV metodom određeni su Sx2- u modelnim otopinama, te u RJ s najvećim koncentracijama u uzorcima ispod kemokline. Praćenjem sezonske dinamike Sx2- pokazano je kako njihova prisutnost i koncentracija ovise o fizikalno – kemijskim i mikrobiološkim čimbenicima. Najveće koncentracije, do 89 μM polisulfidnog S0, određene su tijekom ljeta za vrijeme izraženije raslojenosti vodenog stupca i intenzivnije mikrobiološke aktivnosti kada su dominirale ljubičaste sumporne bakterije (eng. purple sulfur bacteria, PSB), dok tijekom slabije raslojenosti i pojave holomiksije, Sx2- nisu detektirani.The direct analytical determination of polysulfide (Sx2-) in seawater solutions is a challenge due to the low thermodynamic stability constants of Sx2-. To develop and apply a direct method for determining and characterizing Sx2-, its electrochemical behavior was investigated at a mercury (Hg) electrode. The marine euxinic environment of Lake Rogoznica – Zmajevo oko (RL) was chosen as a model for testing the electroanalytical method (EM), differential pulse voltammetry (DPV) for the direct determination of polysulfides under natural conditions. In addition to DPV, cyclic voltammetry (CV) and sampled DC voltammetry/polarography (SDC) were also used to monitor reduced sulfur species (RSS), i.e. Sx2-, as well as other analytical methods: UV/Vis spectrophotometry for additional determination of Sx2- and atomic force microscopy (AFM) and dynamic light scattering (DLS) to monitor changes in RSS properties. The change in cell morphology of phototrophic sulfur bacteria as a source of elemental S under different environmental and experimental conditions was monitored by AFM, while DLS monitored the change in hydrodynamic properties of elemental S under different dilution conditions. The DPV method was used to determine Sx2- in model solutions and the RL water column, with the highest concentrations measured in samples below the chemocline. The observation of the seasonal dynamics of Sx2- showed that its presence and concentration depend on physico-chemical and microbiological factors. The highest concentrations, up to 89 μM polysulfide S0, were determined in summer during pronounced stratification of the water column and intense microbial activity when purple sulfur bacteria (PSB) predominate, while Sx2- was not detected during periods of weak stratification and occurrence of holomixia
Artistic projects based on the use of the industrial heritage of socialism and the question of social politicity of art
No full textU fokusu disertacije nalaze se suvremene društveno angažirane umjetničke prakse
hrvatske umjetnosti koje se bave temom deindustrijalizacije, vrlo složenim društvenim
fenomenom s izrazito političkim predznakom, usko vezanim uz raspad socijalizma i pojam
tranzicije 90-ih godina 20. st. Deindustrijalizacija se u Hrvatskoj odvila u specifičnom
povijesnom trenutku, uokvirena ratnim i poslijeratnim društveno-političkim okolnostima, koje
su, u konačnici, dovele do stigmatizacije socijalističkog nasljeđa, pa slijedom toga i industrijske
baštine vezane uz razdoblje socijalizma. Stoga, kada govorimo o tom, recentnom industrijskom
nasljeđu, mislimo i na, uglavnom neistraženu, nezapisanu recentnu radničku povijest.
Po prirodi odabrane teme i umjetnički radovi koji se bave procesom i društvenim
posljedicama deindustrijalizacije, izrazito su politični, zbog čega je teorijski okvir njihove
interpretacije, generiran objašnjenjima suvremene društveno-angažirane umjetnosti
(Bourriaud, Bishop) proširen konceptima iz područja filozofije politike, a kako bi se artikulirala
osnova za složenije analize suodnosa umjetnosti, društva, estetike i politike. Pristupa im se
oslanjanjem na filozofski diskurs Jacquesa Rancièrea, koji umjetnost i politiku prikazuje kao
međusobno srodna područja, uz dodatna pojašnjenja Rancièreove terminologije od strane
teoretičara Gabriela Rockhilla te fokusiranjem na Rockhillov koncept društvene političnosti
umjetnosti. Njegova operabilnost ispituje na konkretnim primjerima umjetničkih realizacija
inkorporiranim u muzeološko-istraživačke projekte – studije slučaja – vezane uz materijalnu i
nematerijalnu baštinu industrijske proizvodnje i radničke povijesti u razdoblju socijalizma, u
čijoj se interpretaciji isprepleću metode povijesti umjetnosti, industrijskih i baštinskih studija s
filozofijom politike.
Predmet disertacije je kompleksan suodnos umjetnosti, društva, estetike i politike,
onakav kakvog nalazimo u korpusu umjetničkih realizacija na temu deindustrijalizacije, koji se
razmatra u središnjem dijelu rada, kroz prikaz i objašnjenje muzeološko-istraživačkih projekata
vezanih uz tvornice „Dalmatinka“ u Sinju, „Jugoplastiku“ u Splitu i „Željezaru Sisak“ u Sisku,
kao eklatantne primjere deindustrijalizacije u lokalnom kontekstu. Koristeći se umjetničkim
strategijama koje se pozivaju na baštinu povijesne avangarde, promatrane umjetničke prakse i
konkretne umjetničke realizacije, nastale uz navedene muzeološko-istraživačke projekte,
sagledavaju se iz perspektive aktiviranja kolektivnog sjećanja i afirmacije zaboravljenog
industrijskog nasljeđa socijalizma, nadopunjene usporednom analizom uvjeta njihove
produkcije, cirkulacije i recepcije kojima se ispituje društveno-politički potencijal takve vrste
umjetnosti. Uz metodologiju povijesti umjetnosti, u disertaciji su obilato korištene i sociološke
metode i instrumenti (etnografska metoda, polustrukturirani intervju, intervju), a s ciljem
dobivanja, kako uvida u mišljenja umjetnika i kustosa, tako i u stavove i osjećaje radnika,
ključnih aktera procesa deindustrijalizacije. Širenje analitičke i teorijske aparature olakšalo je
preciznije određenje specifičnosti odabranog korpusa utemeljene u Rockhillov koncept
društvene političnosti umjetnosti, na temelju kojeg se ovaj nadaje kao zaseban društvenokritički
iskaz unutar kompleksa suvremene, angažirane umjetnosti.The dissertation focuses on contemporary socially engaged artistic practices of Croatian
art that deal with the topic of deindustrialization, a very complex social phenomenon with an
extremely political sign, closely related to the collapse of socialism and the concept of transition
in the 1990s. Deindustrialization in Croatia took place at a specific historical moment, framed
by war and post-war socio-political circumstances, which ultimately led to the stigmatization
of the socialist heritage, and consequently the industrial heritage related to the period of
socialism. Therefore, when we talk about this recent industrial heritage, we also mean the
largely unexplored, unrecorded recent labor history.
By nature, the selected topics and artworks dealing with the process and social
consequences of deindustrialization are extremely political, which is why the theoretical
framework of their interpretation, generated by the explanations of contemporary socially
engaged art (Bourriaud, Bishop), was expanded with concepts from the field of political
philosophy, and in order to the basis for more complex analyzes of the relationship between art,
society, aesthetics and politics was articulated. They are approached by relying on the
philosophical discourse of Jacques Rancière, which presents art and politics as mutually related
fields, supplemented by additional clarifications of Rancière's terminology by theorist Gabriel
Rockhill and by focusing on Rockhill's concept of the social politics of art. Its operability is
tested on concrete examples of artistic realizations incorporated in museological research
projects - case studies - related to the tangible and intangible heritage of industrial production
and labor history in the period of socialism, in the interpretation of which the methods of art
history, industrial and heritage studies are intertwined with political philosophy.
Her subject is the complex relationship between art, society, aesthetics and politics, such
as we find in the corpus of artistic realizations on the subject of deindustrialization, which is
considered in the central part of the dissertation, through the presentation and explanation of
museological and research projects related to the "Dalmatinka" factories in Sinj, "Jugoplastika"
in Split and "Željezar Sisak" in Sisak, as glaring examples of deindustrialization in the local
context. Using artistic strategies that refer to the heritage of the historical avant-garde, the
observed artistic practices and concrete artistic realizations, created with the aforementioned
museological-research projects, are viewed from the perspective of activating collective
memory and affirming the forgotten industrial heritage of socialism, complemented by a
comparative analysis of the conditions of their production, circulation and receptions that
examine the socio-political potential of this type of art. In addition to the methodology of art
history, sociological methods and instruments (ethnographic method, semi-structured
interview, interview) were used extensively in the dissertation, with the aim of gaining insight
into the opinions of artists and curators, as well as into the attitudes and feelings of workers,
key actors of the deindustrialization process. The expansion of the analytical and theoretical
apparatus facilitated a more precise determination of the specificity of the selected corpus based
on Rockhill's concept of the social politics of art, on the basis of which it qualifies as a separate
socio-critical statement within the complex of contemporary, engaged art
Correlation of voice characteristics and quality of life after thyroidectomy without recurrent laryngeal nerve lesion
No full textKirurški postupak kojim se odstranjuje dio ili cijela štitnjača naziva se tireoidektomija. S obzirom na anatomsku blizinu štitnjače i struktura koje sudjeluju u proizvodnji govora, posebna pažnja tijekom postupka tireoidektomije se posvećuje očuvanju povratnog laringealnog živca s posljedičnim očuvanjem funkcije glasa, govora i gutanja. Usprkos niskom postotku pacijenata s ozljedom povratnog laringealnog živca nakon tireoidektomije (do 5%), vrlo visok postotak pacijenata (do 87%) ipak razvije poremećaj glasa. Promjene u glasu se javljaju iako se objektivnim pretragama ne pronalaze promjene na glasnicama, kako u strukturi, tako i u funkciji. Zbog učestalosti pojave poremećaja glasa, kojem je teško utvrditi uzrok nakon tireoidektomije, ova problematika je od iznimne znanstvene i praktične važnosti.
Prvi cilj ovog istraživanja bio je ispitati tijek oporavka glasa nakon tireoidektomije bez lezije povratnog laringealnog živca, u tri vremenske točke nakon operacije. Osim toga, ciljevi su bili ispitati korelate poremećaja glasa nakon tireoidektomije bez lezije povratnog laringealnog živca te ispitati odnos između kvalitete glasa i kvalitete života nakon tireoidektomije bez lezije povratnog laringealnog živca.
U istraživanju su sudjelovala 292 sudionika koji su bili podvrgnuti tireoidektomiji, a nisu razvili ozljedu povratnog laringealnog živca. Ozljeda je isključena primjenom videostroboskopije. Sudionici su praćeni kroz 4 vremenske točke: preoperativno, između 7 i 10 dana nakon operacije, 3 mjeseca nakon operacije i 6 mjeseci nakon operacije. Oni kojima se glas oporavio bili su isključeni iz sljedećeg mjerenja. U svim mjerenjima su se procjenjivale objektivne, perceptivne i subjektivne značajke glasa te kvaliteta života. Objektivne značajke su se mjerile akustičkom analizom koja je uključivala: fundamentalnu frekvenciju (F0), intenzitet, jitter, shimmer i maksimalno vrijeme fonacije (MVF). Perceptivne značajke su se mjerile ljestvicom GRBAS, a subjektivne VHI ljestvicom. Kvaliteta života se mjerila WHOQOL-BREF ljestvicom te su se koristile ukupna kvaliteta života, zadovoljstvo zdravljem, fizička i psihološka domena kvalitete života. Primijenjen je i sociodemografski upitnik.
Rezultati su pokazali da je čak 85% sudionika razvilo poremećaj glasa nakon tireoidektomije. Rezultati ANOVA-e na ponovljenim mjerenjima, primjenom LOCF metode, su pokazali statistički značajne razlike u kvaliteti objektivnih, perceptivnih i subjektivnih značajki glasa između tri postoperativna mjerenja, s konzistentnim trendom poboljšanja poremećaja glasa uvjetovanih tireoidektomijom. Korelacijska i regresijska analiza su pokazale da je kvaliteta glasa mjerena objektivnim, perceptivnim i subjektivnim mjerama značajno povezana i dobro predviđa ukupnu kvalitetu života, zadovoljstvo zdravljem te fizičku i psihološku domenu kvalitete života u sva tri postoperativna mjerenja. Niža kvaliteta glasa rezultirala je i nižom procjenom kvalitete života u ovim domenama. Vrsta i trajanje operacije, preoperativni volumen štitnjače te BMI sudionika pokazali su se važnim prediktorima brzine oporavka glasa, pri čemu su se sudionici podvrgnuti totalnoj tireoidektomiji (nasuprot lobektomiji), oni kod kojih je operacija duže trajala, oni s većim volumenom štitnjače i višim BMI-om oporavljali sporije.Introduction: In recent decades, the number of people with thyroid diseases requiring surgical treatment has been continuously growing. Thyroidectomy is a surgical procedure that removes part (lobectomy) or all of the thyroid gland (total thyroidectomy). Considering the anatomical proximity of the thyroid gland and the structures involved in speech production, special attention during the thyroidectomy procedure is devoted to the preservation of the recurrent laryngeal nerve with the consequent preservation of voice, speech and swallowing function. Despite the low percentage of patients with recurrent laryngeal nerve injury after thyroidectomy (up to 5%), a very high percentage of patients (up to 87%) still develop a voice disorder. Changes in the voice occur even though objective tests do not find changes in the vocal cords, both in structure and function. Longitudinal studies showed that, with time, most of the patients recover, however high percentage of patients (up to 18%) can have a voice disorder that persists even one year after thyroidectomy. Considering that voice has an important role in personal identity, a changed voice, especially if the condition is long-term, can cause increased anxiety and depression, lower the quality of life, and slow down the recovery process. Some of previously examined risk factors for voice disorder development and persistence include age, sex, cigarette and alcohol consumption, BMI, type of surgery, time of surgery and volume of thyroid gland before surgery, however results were inconsistent.
Due to the frequency of voice disorder occurrence after thyroidectomy, there is an exceptional scientific and practical importance of studying patients without visible vocal cords injuries. Therefore, the main aim of this study was to follow recovery of the voice disorder that developed without recurrent laryngeal nerve injury. The first objective was to examine the course of voice recovery at three time points after surgery: 7 to 10 days, 3 months, and 6 months after the surgery. Second objective were to examine relationship between voice quality and quality of life after thyroidectomy. Finally, third objective was to determine the correlates of voice disorders after thyroidectomy without recurrent laryngeal nerve lesion.
Methodology: Participants of the study were 292 patients who underwent thyroidectomy and did not develop an injury to the recurrent laryngeal nerve. Initial sample size was 350, but 58 participants were excluded due to voice disorder before surgery, recurrent laryngeal nerve and giving up. Recurrent laryngeal nerve injury was ruled out using videostroboscopy. Participants who entered the study were followed through 4 time points: preoperatively, between 7 and 10 days after the surgery, 3 months after the surgery, and 6 months after the surgery. Those whose voice recovered were excluded from the next measurement. In all measurements, objective, perceptive and subjective features of the voice, as well as quality of life were assessed. Objective features were measured by acoustic analysis that included Fundamental Frequency (F0), Intensity, Jitter, Shimmer and Maximum Phonation Time (MVF). Perceptive features were measured with the GRBAS scale, and subjective features with the Voice Handicap index (VHI) scale. Quality of life was measured by the WHOQOL-BREF questionnaire. Overall quality of life, health satisfaction, physical and psychological domains of quality of life were used. Besides that, a sociodemographic questionnaire, that included questions about age, sex, profession was also applied.
Results: The results showed that as many as 85% of the participants developed a voice disorder after thyroidectomy without recurrent laryngeal nerve injury. 3 months after surgery, 52% of participants still suffered from disorder, and 6 months after surgery, 22% of them still didn’t fully recover. The results of repeated measures ANOVA, using the LOCF (last observation carried forward) method, showed statistically significant differences in the quality of objective, perceptive and subjective features of the voice between the three postoperative time points, with a consistent trend of improvement in voice quality. Most of objective, perceptive, and subjective indicators of voice quality were significantly correlated with overall quality of life, health satisfaction, physical and psychological domains of quality of life in all three postoperative measurements. Also, those indicators proved to be significant predictors of all examined domains of life quality, with the highest level of prediction 3 months after surgery. The bigger changes in voice resulted with lower subjective quality of life in all observed domains. Type and duration of surgery, preoperative thyroid volume, and participants' BMI were found to be important predictors of the rate of voice recovery. Participants undergoing total thyroidectomy were recovering in a slower rate than participants that had lobectomy. Furthermore, longer surgery and bigger thyroid volume resulted with slower recovery of voice, as well as higher BMI.
Conclusion: Voice disorders are common after thyroid surgery even when there is no laryngeal nerve injury. Although, a significant improvement can be observed over the period of time, approximately one-fifth of patients who develop the disorder, have it even 6 months after the surgery. Voice disorder is significantly correlated with the overall quality of life, satisfaction with health, physical and psychological domains of life quality. The most important factors for the persistence od voice disorder relate to the type and duration of the surgery, while the preoperative thyroid volume and the patient's BMI had significant, but smaller effect. Results emphasize the need for more systematic research, and developing standardized protocols and methodology for studying voice disorders after thyroidectomy. Systematic study and consistent results are necessary first step in developing prevention and rehabilitation programs
Expression of candidate genes for congenital anomalies of the kidney and urinary tract, FGFR1, FGFR2 and RIP5, during fetal and postnatal development in humans and mice
No full textPrirođene anomalije bubrega i urotrakta (CAKUT) doprinose u oko 23% porođajnih abnormalnosti i odgovoran je za približno 50% pedijatrijskih slučajeva i 7% slučajeva završnog stadija bubrežne bolesti u odraslih diljem svijeta. Morfogeneza, razvoj i sazrijevanje bubrega složeni su procesi koordinirani međuodnosima mnogih gena. Do danas, monogenetske abnormalnosti povezane s CAKUT-om uključuju mutacije u više od 30 gena i otkrivene su u malom postotku (12%) istraženih slučajeva, s nedostatnim dokazima o njihovoj uzročnoj povezanosti. Prethodno provedena istraživanja pokazala su da su Receptori fibroblastnih čimbenika rasta 1 i 2 (FGFR1 i FGFR2) i Protein kinaza koja djeluje na receptor 5 (RIP5) potencijalni kandidat geni čija je mutacija odgovorna za nastanak prirođenih anomalija bubrega i mokraćnog sustava sindromskog ili izoliranog tipa. Stoga je cilj ovog istraživanja bio odrediti prostorno-vremenski obrazac navedenih proteina u modelu yotari (Dab1-/-) miša te u zdravim ljudskim bubrezima u razvoju i bubrezima zahvaćenim CAKUT-om (bubrezi udvostručenog uretera (DU), hipoplastični bubrezi (HYP), displastični bubrezi (DYS)) od 22. do 41. tjedna fetalnog razvoja, kako bismo utvrdili kako je potencijalna promjena izražaja gena i njihovih proteina povezana s pojavom CAKUT-a. Koristeći model Dab1-/- miša, opisali smo značajne razlike u obrascima prostorno- vremenskog izražaja FGFR1, FGFR2, RIP5 u embrionalnim i postnatalnim razvojnim fazama. Činjenica da je izražaj navedenih proteina zapažen u svim istraživanim fazama razvoja bubrega implicira njihovu ključnu ulogu u ranoj diferencijaciji metanefrogenog mezoderma, grananju mokraćovodnog pupoljka, nefrogenezi i preživljavanju nefron progenitora. Obzirom da su FGFR1, FGFR2 i RIP5 izraženi u svim dijelovima nefrona a neki od njih i u bubrežnoj vaskulaturi, opravdano je nagađati o njihovom značaju u održavanju homeostaze i sazrijevanju bubrega kao i o njihovoj ulozi u nastanku različitih bubrežnih patologija. Ipak, točan mehanizam putem kojeg Reelin/Dab1 put utječe na izražaj ispitivanih markera tek treba razjasniti. Smanjenje izražaja Erk1/2 i mTORa u bubrezima yotari miša može se objasniti predloženim signalnim putom u kojem je Dab1 samo djelomično uključen u MEK/Erk1/2 aktivaciju posredovanu Reelinom. Utjecaj CAKUT kandidat-gena na nefrogenezu i bubrežnu funkciju zdravih ljudskih bubrega u razvoju i bubrega zahvaćenih CAKUT-om potkrijepljen je značajnim varijacijama u prostorno-vremenskom obrascu izražaja ispitivanih markera. Izražaj FGFR1 i FGFR2 mRNA i njihovih proteina koji su značajno viši u citoplazmatskoj i jezgrinoj regiji stanica bubrega zahvaćenih CAKUT-om nego u normalnom tkivu, te promijenjena dinamika izražaja ispitivanih proteina, sugerira da je aktivacija FGF signalnog puta kritičan događaj u patogenezi prirođenih anomalija bubrega i urotrakta. Smanjeni izražaj RIP5 tijekom istraživanih razvojnih razdoblja ne može se pripisati očekivanim razinama apoptoze u hipoplastičnim i displastičnim bubrezima, što ukazuje da je proces apoptoze reguliran alternativnim signalnim putevima. Naši rezultati naglašavaju kritičnu ulogu istraživanih markera tijekom normalnog razvoja bubrega i njihovu potencijalnu ulogu u bubrežnoj patologiji i dijagnostici, gdje bi mogli poslužiti kao biomarkeri i terapijski ciljevi. Daljnja istraživanja su potrebna kako bi se okarakterizirala uloga ispitivanih gena i proteina u regulaciji diferencijacije bubrega, što bi moglo poboljšati pristup personaliziranoj medicini prirođenih anomalija bubrega i mokraćovodnog puta.Congenital anomalies of the kidney and urinary tract (CAKUT) account for 23% of congenital anomalies at birth and are implicated in roughly 50% of pediatric cases and 7% of cases of end-stage kidney disease in adults globally. The development, maturation, and morphogenesis of kidneys are intricate processes influenced by numerous genes. So far, monogenic abnormalities linked with CAKUT involve mutations in over 30 genes, identified in a limited proportion (12%) of examined cases, with insufficient evidence to establish their direct causal relationship. Previously conducted research has shown that Fibroblast Growth Factor Receptors 1 and 2 (FGFR1 and FGFR2) and Receptor-interacting protein kinase 5 (RIP5) are potential candidate genes that may lead to the development of congenital anomalies of the kidneys and urinary system, either in a syndromic or isolated form. Hence, the objective of this study was to examine the spatial and temporal distribution of the specified proteins in the yotari (Dab1-/-) mouse model, as well as in normally developing human kidneys and those affected by CAKUT (including duplex (DU) kidneys, hypoplastic kidneys (HYP), and dysplastic kidneys (DYS)), spanning from the 22nd to the 41st week of fetal development. This investigation aimed to discern the potential correlation between gene and protein expression alterations and the onset of CAKUT. Utilizing the Dab1-/- mouse model, we identified notable discrepancies in the spatio- temporal expression profiles of FGFR1, FGFR2, and RIP5 during embryonic and postnatal developmental phases. The consistent expression of these proteins across all examined stages of kidney development suggests their critical involvement in the early differentiation of the metanephrogenic mesoderm, ureteric bud branching, nephrogenesis, and the viability of nephron progenitors. Given their expression in various segments of the nephron and some within the renal vasculature, it is reasonable to speculate about their significance in maintaining overall kidney homeostasis and maturation, as well as their potential role in the genesis of diverse renal pathologies. The precise mechanism through which the Reelin/Dab1 signalling pathway influences the expression of the examined markers remains unclear. The reduction in Erk1/2 and mTOR expression in the kidneys of yotari mice may be attributed to a proposed signaling pathway where Dab1 is only partially involved in MEK/Erk1/2 activation mediated by Reelin. The impact of CAKUT candidate genes on nephrogenesis and renal function in normally developing human kidneys and those affected by CAKUT is supported by significant variations in the spatio-temporal expression patterns of the investigated markers. The elevated expression of FGFR1 and FGFR2 mRNA and proteins, particularly in the cytoplasmic and nuclear regions of CAKUT-affected kidney cells compared to normal tissue, along with altered dynamics in the expression of the examined proteins, suggests that activation of the FGF signaling pathway plays a crucial role in the pathogenesis of congenital kidney anomalies and urinary tract issues. The decreased expression of RIP5 during the developmental periods under investigation cannot solely be attributed to the expected levels of apoptosis in hypoplastic and dysplastic kidneys, indicating that other signaling pathways regulate the apoptosis process. Our findings underscore the pivotal role of the investigated markers in normal kidney development and their potential significance in renal pathology and diagnostics, where they could serve as biomarkers and therapeutic targets. Further research is warranted to delineate their roles in regulating renal differentiation, thereby enhancing personalized medicine approaches for congenital kidney and urinary tract anomalies
Prognostic significance of gene BIRC5 polymorphisms and expressions of isoforms in oral and oropharyngeal squamous cell carcinoma
No full textCilj istraživanja: Odrediti ekspresiju različitih izoformi gena BIRC5 u tumorskom tkivu
pacijenata s pločastim karcinomom usne šupljine i orofarinksa u usporedbi s tkivom zdravih
kontrola. Odrediti polimorfizme gena BIRC5 iz uzoraka krvi bolesnika i zdravih kontrola, te
usporediti njihove korelacije kao i korelacije s kliničko patohistološkim parametrima.
Nacrt studije: Istraživanje je postavljeno kao retrospektivna studija.
Ispitanici i metode: U istraživanje su uključeni bolesnici kod kojih je patohistološki potvrđen
pločasti karcinom usne šupljine i orofarinksa. Kao kontrolna skupina korišteni su uzorci
bukalne sluznice i periferne krvi pacijenata koji su liječeni na Zavodu za maksilofacijalnu i
oralnu kirurgiju, zbog neke druge nemaligne bolesti. Iz krvi je izolirana genomska DNK za
analizu polimorfizama metodama PCR, analizom heterodupleksa i sekvenciranjem, a ekspresije
izoformi određivane su metodom qPCR iz ukupne RNK tumorskih uzoraka i uzoraka zdrave
sluznice.
Rezultati: Ukupno je ispitivano osam izoformi gena BIRC5 čije su relativne ekspresije
pronađene i u tumorskom tkivu kao i u uzorcima zdravih kontrola. Sve izoforme statistički
značajnije su izraženije u tumorskom tkivu, s tim da su najizraženije izoforme S wt, S 2α i S
2B. U usporedbi s kliničko-patološkim parametrima statistički značajnom pokazala se je
relativna ekspresija izoforme S Δex3 u orofaringealnih sijela, kao i kod uznapredovalijih
kliničkih stadija (III. i IV.) oba tumorska sijela. Nadalje, nađeno je ukupno 17 polimorfizama,
od kojih se 11 pojavilo u tumorima usne šupljine i orofarinksa s učestalošću rjeđih alela (MAF)
većom od 5%. Pet polimorfizama (c.-1547C>T, c.-31G>C, c.385G>A, c.*148T>C,
c.*1373C>A) značajno je povezano s veličinom tumora, stadijem tumora i pozitivnim limfnim
čvorovima.
Zaključak: Survivin, proteinski produkt gena BIRC5, potencijalni je biomarker agresivnosti ili
pokazatelja ishoda liječenja kod oboljelih od pločastog karcinoma usne šupljine i orofarinska.
Sve izoforme survivina jače su eksprimirane u tumorskim tkivima, a njihova se ekspresija
uglavnom ne može povezati s kliničko patološkim parametrima, osim izoforme S Δex3.
Rezultati pokazuju da ovi BIRC5 polimorfizmi nemaju značajan utjecaj na preživljenje
bolesnika te usmjeravaju pažnju na daljnja istraživanja povezana s ekspresijom pojedinih
izoformi ovog gena, kao što je izoforma S Δex3, s progresijom HNSCC-a.Objectives: To determine the expression of different isoforms of the gene BIRC5 in the tumor
tissue of patients with oral and oropharyngeal squamous cell carcinoma compared to the tissue
of healthy controls. To determine gene BIRC5 polymorphisms from blood samples of patients
and healthy controls, and to compare their correlations as well as correlations with clinical
pathohistological parameters.
Study design: The research was designed as a retrospective study.
Participants and methods: The study included patients with pathohistologically confirmed
oral and oropharyngeal squamous cell carcinoma. As a control group, samples of buccal mucosa
and peripheral blood of patients who were treated at the Department of Maxillofacial and Oral
Surgery for some other non-malignant diseases were used. Genomic DNA was isolated from
blood for analysis of polymorphisms by PCR, heteroduplex analysis and sequencing, and
isoform expressions were determined by qPCR from total RNA of tumor samples and samples
of healthy mucosa.
Results: A total of eight isoforms of the BIRC5 gene were examined, whose relative
expressions were found both in tumor tissue and in healthy control samples. All isoforms are
statistically significantly more expressed in tumor tissue, with the most expressed isoforms
being S wt, S 2α and S 2B. In comparison with the clinical and pathological parameters, the
relative expression of the S Δex3 isoform in oropharyngeal lesions, as well as in advanced
clinical stages (III and IV) of both tumor lesions, was statistically significant. Furthermore, a
total of 17 polymorphisms were found, of which 11 appeared in tumors of the oral cavity and
oropharynx with a minor allele frequency (MAF) greater than 5%.
Conclusion: Survivin, the protein product of the BIRC5 gene, is a potential biomarker of
aggressiveness or an indicator of the outcome of treatment in patients with oral and
oropharyngeal squamous cell carcinoma. All isoforms of survivin are more strongly expressed
in tumor tissues, and their expression generally cannot be corelate with clinical-pathological
parameters, except isoform S Δex3. Five polymorphisms (c.-1547C>T, c.-31G>C, c.385G>A,
c.*148T>C, c.*1373C>A) were significantly associated with tumor size, tumor stage and
positive lymph nodes . The results show that these BIRC5 polymorphisms do not have a
significant impact on patient survival and suggest for further research related to the expression
of individual isoforms of this gene, such as the S Δex3 isoform, with the progression of HNSCC
Structural analysis of blood plasma N-glycome from a long-lived naked mole-rat (Heterocephalus glaber Rüppell, 1842)
No full textGolokrtičasti štakor (GŠ) (Heterocephalus glaber Rüppell, 1842) je eusocijalni fosorijalni glodavac čiji je prirodni areal Istočna Afrika, a zbog životnog vijeka koji prelazi 30 godina je atraktivan modelni organizam u biologiji starenja. Molekularni mehanizmi otpornosti na kancerogenezu, neurodegeneraciju, hipoksiju i neke vrste boli povezani su sa održavanjem proteostaze u čemu sudjeluju i posttranslacijske modifikacije proteina. Dinamika i raznolikost glikozilacije proteina u GŠ do sada nije istraživana. U ovom je radu pomoću tekućinske kromatografije i spektrometrije masa provedena strukturna analiza N-glikoma krvne plazme GŠ. Određene su strukture i udjeli 160 različitih N-glikana među kojima se ističe strukturni motiv 4-O-acetilacije sijalinskih kiselina. Glikoproteomskom analizom otkriveno je da takvi sijaloglikani potječu s inhibitora proteaza u krvnoj plazmi te je pretpostavljen njihov zaštitni i stabilizirajući utjecaj na proteine.The naked mole-rat (NMR) (Heterocephalus glaber Rüppell, 1842) is an eusocial fossorial rodent native to East Africa. Its exceptionally long lifespan of over 30 years makes it a popular non-conventional model organism in the biology of ageing and
longevity. Molecular mechanisms underlying resistance to cancerogenesis, neurodegeneration, hypoxia and certain types of pain are related to the maintenance of proteostasis where key players are protein post-translational modifications. The dynamics and diversity of protein glycosylation in NMR are completely unexplored. In this study, a structural analysis of NMR blood plasma N-glycome was performed using liquid chromatography and mass spectrometry. A total od 160 different N-glycans were annotated and quantified. The core structural motif in the N-glycome of NMR was the presence of 4-O-acetylated sialic acids. Employing a glycoproteomic analysis, 4-Oacetylated sialo-N-glycans were pinpointed to plasma protease inhibitors and their protective and stabilizing effect on the proteins was inferred
Difference in reproduction, discrimination and production of perceived and presented time intervals
No full textTajming, tj. percepcija i procesiranje vremenskih intervala, označava subjektivno iskustvo prolaženja fizičkog vremena te interpretaciju trajanja događaja, a od ključnog je značaja za kognitivno, perceptivno i motoričko funkcioniranje čovjeka.
Cilj rada bio je istražiti razlike u procesiranju vremenskih intervala u rasponu milisekundi i sekundi na temelju eksperimentalnih paradigmi reprodukcije, diskriminacije i produkcije vremenskih intervala, kako bi se dobili dokazi u prilog teoriji o jednom namjenskom (zajedničkom) mehanizmu ili intrinzičnim mehanizmima (više lokalnih mehanizama) mjerenja vremena u mozgu. U istraživanju je sudjelovalo 115 sudionika u dobi od 19-24 godine. Pokazatelje izvedbi tajminga predstavljale su vrijednosti varijabilnosti (SD i CV) i preciznosti (AI), a u daljnjim inferencijalnim analizama te su vrijednosti predstavljale zavisne varijable.
Rezultati pokazuju kako se varijabilnost izvedbi navedenih paradigmi tajminga statistički značajno razlikuje (F(1.43, 143.01) = 264.10, p < .001, ηp 2 = .73) u korist motoričkoga tajminga, koji se pokazao kao najstabilniji, dok se perceptivni tajming pokazao kao najvarijabilniji. U produkciji intervala pronađena je veća varijabilnost intervala kraćih od sekunde (F(1, 104) = 164.11, p < .001, ηp 2 = .61) i značajna povezanost unutar pojedinih skupova pokazatelja izvedbi, no ne i između jednog i drugog skupa. Pokazalo se kako radno pamćenje nije povezano s pokazateljima izvedbi u paradigmama reprodukcije i produkcije intervala, a konkurentni zadatak uzrokuje povećanje varijabilnosti motoričkog (automatskog) tajminga (F(1,90) = 122.47, p < .001, ηp 2 = .58). O rezultatima se raspravlja u bihevioralnom kontekstu eksperimenta, ali i uz korištenje argumenata iz neurobioloških teorija i istraživanja. Općenito gledano, rezultati govore u prilog teorijama prema kojima je procesiranje vremenskih intervala pod kontrolom specijaliziranih i distribuiranih mreža, a ne centralnog sata.Timing, or the perception and processing of time intervals, refers to the subjective experience of physical time and the interpretation of event durations. It plays a crucial role in an individual's cognitive, perceptual, and motor functions. Current research aimed to explore differences in the processing of time intervals, ranging from milliseconds to seconds, using experimental paradigms involving reproduction, discrimination, and production of time intervals. The goal was to gather evidence supporting either a single dedicated mechanism (common timing) or multiple intrinsic mechanisms (local timing) for time measurement in the brain. A total of 115 participants, aged 19-24, took part in the study. Timing performance was assessed using indicators of variability (SD and CV) and precision (AI), which served as dependent variables in further inferential analyses. The findings revealed statistically significant differences in performance variability across the timing paradigms (F(1.43, 143.01) = 264.10, p < .001, ηp 2 = .73), with motor timing emerging as the most stable and perceptual timing as the most variable. Greater variability was observed in the production of intervals shorter than one second (F(1,
104) = 164.11, p < .001, ηp 2 = .61), alongside significant relationships within individual sets of performance measures, though not between the two sets. Additionally, working memory was found to be unrelated to performance in the interval
reproduction and production paradigms. However, introducing a competitive task increased the variability of motor (automatic) timing (F(1,90) = 122.47, p < .001, ηp 2 = .58). The results are discussed concerning the behavioral context of the experiment and supported by neurobiological theories. Overall, the findings suggest that the timing is governed by specialized, distributed networks in the brain, rather than by a central clock
The concept of madness through Michel Foucault's interpretation
No full textGlavni je cilj rada pokazati promjenjivu prirodu fenomena ludila analizom povijesnih zapisa o ludilu, a potom oprimjeriti recentnu raspravu o duševnom poremećaju. Širi cilj rada jest filozofski istražiti i prosuditi povijesnu i suvremenu psihijatrijsku praksu, a pojmove bolesti i zdravlja, odnosno duševnog poremećaja, promatrati kao kategorije s praktičnim posljedicama koje se ogledaju u medikalizaciji života uopće. Razmatranja u radu pod utjecajem su autora Michela Foucaulta koji fenomen ludila prati (tumači i interpretira) od srednjega vijeka pa do klasicizma, kada se ludilo izražava i unificira kao duševna bolest. Foucault će tvrditi da psihijatrijska praksa nastaje kao odgovor na zamijećenu devijantnost među europskim stanovništvom, stoga je uloga prve psihijatrije kontrolirati i isključivati, a potom upitnim terapeutikama liječiti. Prema tome, imenovanje nekog stanja duševnim poremećajem ovisno je o društveno-kulturnim prilikama pa je opravdana primjedba o nejasnom stvarnom početku bolesti. Rad u pozadini implicitno propituje autorove teze, poput uvjeta u kojemu nastaje psihijatrijsko znanje, načina na koji se putem ono jezika simulira i točke u kojoj se takvo znanje zaustavlja. U radu se koristi izraz ludilo do trenutka rađanja psihijatrije kao znanosti u 19. stoljeću, kada se pojam mijenja u sintagmu duševni poremećaj. Danas važeća perspektiva biologijske psihijatrije koja dominira kad psihosocijalnom primarno se okreće prema farmakološkim intervencijama za ljudska stanja u kojima je kudikamo nejasna granica je li stanje patologija ili životni problem. Dio je rada posvećen ključnim psihijatrijskim pojmovima i izazovima, poput relativnosti dijagnoza i redukcionizma, na koji se nastavlja rasprava filozofije psihijatrije. Usprkos naporima suvremene psihijatrije za pronalaskom objektivnih (etioloških) objašnjenja za poremećaj psihijatrijske dijagnoze dalje su najproblematičniji moment psihijatrije.The main goal of this paper is to show the changing nature of the phenomenon of insanity by analyzing (historical) records of insanity, and then exemplify the recent debate on mental disorders. The broader goal of the paper is to philosophically research and evaluate the historical and current psychiatric practice, and to observe the concepts of illness and health, that is, mental disorder as categories with practical consequences that are reflected in the medicalization of life in general. The reflection in this paper is influenced by the author Michel Foucault, who follows (interprets) the phenomenon of madness from the Middle Ages to the time of Classicism, when madness is expressed and unified into mental illness. Foucault claims that psychiatric practice arises as a response to perceived deviance among the European population, therefore the role of psychiatry is first to control and exclude, and then to treat with questionable therapeutics. Therefore, the designation of a condition as a mental disorder depends on socio-cultural circumstances, so the objection about the unclear actual onset of the disease is justified. In its background, the paper implicitly questions the author's theses, such as the conditions in which psychiatric knowledge is created, the way in which it is simulated through language, and the point at which such knowledge stops. The paper uses the term insanity until the birth of psychiatry as a science in the 19th century, when the term was changed to the phrase mental disorder. Today, the valid perspective of biological psychiatry, which dominates the psychosocial field, primarily turns to pharmacological interventions for human conditions in which the boundary is somewhat unclear whether the condition is a pathology or a life problem. Part of the paper is devoted to key psychiatric concepts and challenges such as the relativity of diagnoses and reductionism, which is continued in the discussion of the philosophy of psychiatry. Despite the efforts of modern psychiatry to find objective (etiological) explanations for the disorder, psychiatric diagnoses are still the most problematic moment of psychiatry
Regularization methods that include experts’ domain knowledge for feature selection in a linear regression model
No full textOvo istraživanje imalo je cilj razviti metodu za odabir znaˇcajki u linearnom regresijskom mo- delu koja u regularizaciju ukljuˇcuje domensko znanje struˇcnjaka o utjecaju ulaznih znaˇcajki na izlaznu, pri ˇcemu se razlikovalo dva naˇcina ukljuˇcivanja znanja struˇcnjaka – deterministiˇcki i metaheuristiˇcki. Predložena metoda se evaluirala na podacima o troškovima energije i karak- teristikama zgrada javnog sektora Republike Hrvatske te na tri scenarija simuliranih podataka iz literature. Za evaluaciju su se koristile mjere uspješnosti predikcije (korigirani koeficijent determinacije, RMSE, MAE i SMAPE) te, u sluˇcaju simuliranih podataka, razlika izme ¯du stvar- nih i procijenjenih regresijskih koeficijenata. Metoda je uspore ¯dena s regularizacijom koja ne ukljuˇcuje domensko znanje struˇcnjaka te s regresijskim stablima. Rezultati na stvarnim poda- cima pokazuju da je uvo ¯denje domenskog znanja struˇcnjaka metaheuristiˇckim pristupom re- zultiralo poboljšanjem uspješnosti predikcije u odnosu na spomenute metode, dok je uvo ¯denje domenskog znanja struˇcnjaka deterministiˇckim pristupom u nekim sluˇcajevima rezultiralo po- boljšanjem uspješnosti predikcije. U okviru simulacijskog eksperimenta, uvo ¯denje domenskog znanja struˇcnjaka rezultiralo je poboljšanjem nekih mjera uspješnosti predikcije u odnosu na regularizaciju koja ne koristi znanje struˇcnjaka samo kod metaheuristiˇckog pristupa, dok pred- ložena metoda uvo ¯denja domenskog znanja struˇcnjaka u regularizaciju nije rezultirala uspješ- nijom predikcijom od metode regresijskih stabala niti za jedan pristup uvo ¯denja domenskog znanja struˇcnjaka. Rezultati pokazuju da razliˇciti naˇcini procjene penalizacijskih koeficijenta i sama struktura modela utjeˇcu na varijabilnost i pristranost modela. Ujedno, otvaraju daljnja pitanja u smislu kako posti´ci i da za kompleksnije skupove podataka domensko znanje struˇc- njaka doprinese smanjenju varijabilnosti i / ili pristranosti modela te poboljšanju uspješnosti predikcije.This research aimed to develop a feature selection method for a linear regression model that in- corporates experts’ domain knowledge about the impact of input features on the output into the regularization process. Two methods of incorporating experts’ knowledge were distinguished: deterministic and metaheuristic. The proposed method was evaluated using data on energy costs and characteristics of public sector buildings in the Republic of Croatia, as well as three scena- rios of simulated data from the literature. Evaluation measures included prediction performance metrics (adjusted coefficient of determination, RMSE, MAE, and SMAPE) and, in the case of simulated data, the difference between actual and estimated regression coefficients. The met- hod was compared to regularization that does not include experts’ domain knowledge and to regression trees. The results on real data indicate that incorporating experts’ domain knowledge through a metaheuristic approach improved prediction performance compared to the mentioned methods, while incorporating domain knowledge through a deterministic approach improved prediction performance in certain cases. In the simulation experiment, introducing experts’ do- main knowledge improved some prediction performance measures over regularization without experts’ knowledge only with the metaheuristic approach, while the proposed method of in- troducing experts’ knowledge into regularization did not outperform the decision tree method in prediction for any approach of introducing experts’ knowledge. The results indicate that different ways of estimating penalization coefficients and the model structure itself affect the variability and bias of the model. Additionally, they raise further questions about how to ac- hieve improved prediction performance and reduced variability and / or bias by incorporating experts’ domain knowledge in more complex data sets
BIOLOGICAL AND CHEMICAL RESPONSES OF SEA SURFACE LAYER TO ATMOSPHERIC DEPOSITION
No full textOva interdisciplinarna studija provedena je s ciljem boljeg razumijevanja učinaka atmosferskog taloženja (AT) na kompleksne strukturne i fiziološke odgovore primarno fitoplanktona te posljedično na promjene kemijskih svojstava površinskog sloja mora i obogaćenje površinskog mikrosloja organskom tvari (OT) na granici faza more-atmosfera. Rad obuhvaća ispitivanja: i) promjenjivosti koncentracija, izvora i taložnih tokova atmosferskih sastavnica te utjecaja AT na plankton i kemiju površinskih slojeva mora na obalnom području srednjeg Jadrana; ii) utjecaja taloženja atmosferskog onečišćenja različitih izvora na planktonsku populaciju te promjenu kemijskih svojstava površinskih slojeva mora kroz prvi inkubacijski eksperiment ovakve vrste na Jadranskom moru; iii) mehanizama kojima sastavnice antropogenog AT utječu na fitoplankton na razini vrsta kroz laboratorijska ispitivanja na fitoplanktonskim monokulturama. Dobiveni rezultati ukazuju da AT, unosom hranjivih i toksičnih tvari, mijenja sastav površinskih slojeva mora čime snažno utječe na kompetitivnost, stopu rasta te strukturu obitavajućih planktonskih zajednica. Takve promjene rezultiraju kvalitativnim i kvantitativnim promjenama biogene OT na morskoj površini, koja akumulacijom na granici faza modificira procese izmjene između mora i atmosfere, što može imati značajne posljedice na biogeokemijsko kruženje tvari te klimu općenito.The main aim of this interdisciplinary study is to gain insight into the effects of atmospheric deposition (AD) on complex structural and physiological responses, primarily of phytoplankton communities, and consequently on the chemical properties of sea surface layers, and the organic matter (OM) enrichment in the sea surface microlayer at the sea-atmosphere interface. Several aspects were examined: i) the variability of concentrations, sources, and deposition fluxes of atmospheric constituents and the impact of AD on the plankton population, and the chemistry of the sea surface layers in the central Adriatic coastal area; ii) the impact of ambient AD from diverse sources on the plankton population, and the change in the chemical properties of the sea surface layers through the first incubation experiment of this kind in the Adriatic Sea; iii) the mechanisms by which the specific anthropogenic AD constituents affect phytoplankton at the level of individual species, through laboratory tests on phytoplankton monocultures. The results obtained indicate that AD alters the composition of the sea surface through the addition of nutrients and toxic components, which strongly affects the competitiveness, growth rate, and thus the structure of the inhabiting plankton communities. Such changes ultimately lead to qualitative and quantitative variations in biogenic OM within the sea surface, whose enhanced enrichment at the natural phase boundary alters ocean-atmosphere exchange processes. The results of this thesis imply that the effects of AD on the sea surface could have strong implications for biogeochemical processes and climate in general