The effects of mutant Ras proteins on the cell signalome

The genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells. © 2020, The Author(s)

Uloge epigenetskih modifikacija u embrionalnoj i adultnoj neurogenezi

The entire nervous system develops from common neural stem cells (NSCs) that line the neural tube during the first weeks of embryonic development. NSCs are self-renewing, multipotent cells that generate neural progenitor cells by asymmetric division, and which, through a limited number of divisions, differentiate into specialized cells of the nervous system: neurons, oligodendrocytes, and astrocytes. Although most neurons are generated before birth, it has been shown that under the influence of appropriate stimuli, in adult mammals and humans, neurogenesis continues throughout life in limited regions of the brain; the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone of the lateral ventricles. Generation of neurons from NSCs encompasses successive stages of progenitor expansion, differentiation, maturation, and integration of new-born neurons into functional neural circuits. Numerous intrinsic and extrinsic factors are involved in the regulation of neurogenesis, forming a complex network of signalling pathways. It seems that epigenetic modifications and their cooperation play an integral role in the precise control of gene expression, which is crucial for the proper acquisition of neural fate. This review will comprehensively summarize the hitherto known roles of epigenetic modifications, in particular DNA modifications, histone modifications and non-coding RNA molecules, in regulating both embryonic and adult neurogenesis in the vertebrate CNS, as well as their mutual mechanisms of cooperation. Further elucidation of the role of epigenetic mechanisms in the process of neurogenesis could lead to the development of novel therapies needed for the treatment of neurodevelopmental and neurodegenerative disorders.Čitav živčani sustav razvija se iz zajedničkih neuralnih matičnih stanica (eng. neural stem cells, NSCs) koje oblažu neuralnu cijev tijekom prvih tjedana embrionalnog razvoja. NSCs su samoobnavljajuće, multipotentne stanice koje asimetričnom diobom generiraju neuralne progenitorske stanice, a koje kroz ograničen broj dioba diferenciraju u specijalizirane stanice živčanog sustava: neurone, oligodendrocite i astrocite. Iako većina neurona nastaje prije rođenja, dokazano je da se pod utjecajem odgovarajućih podražaja, u odraslih sisavaca i čovjeka, neurogeneza nastavlja tijekom cijeloga života u ograničenim regijama mozga; subgranularnoj zoni dentatnog gyrus-a u hipokampusu i subventrikularnoj zoni bočnih ventrikula. Stvaranje neurona iz NSCs uključuje uzastopne faze ekspanzije progenitora, diferencijaciju, sazrijevanje i integraciju novih neurona u funkcionalne neuralne krugove. U regulaciji neurogeneze sudjeluju brojni unutarnji i vanjski čimbenici, tvoreći kompleksnu mrežu signalnih puteva. Čini se da upravo epigenetske modifikacije te njihova međusobna suradnja igra sastavnu ulogu u preciznoj kontroli genske ekspresije ključnoj za pravilno usmjeravanje NSCs u stjecanje neuralne sudbine. Ovaj pregledni rad sveobuhvatno će sažeti do sad poznate uloge epigenetskih modifikacija, točnije DNA modifikacija, histonskih modifikacija i nekodirajućih RNA molekula, u regulaciji embrionalne i odrasle neurogeneze u centralnom živčanom sustavu kralježnjaka, kao i njihove međusobne mehanizme suradnje. Daljnje rasvjetljivanje uloga epigenetskih mehanizama u procesu neurogeneze mogao bi dovesti do razvoja novih terapija za liječenje neurorazvojnih i neurodegenerativnih poremećaja

Cultivation and use of different species of hawthorn (Crataegus spp.)

V rod Crataegus uvrščamo približno 250 rastlinskih vrst. Vrste gloga, ki so v Sloveniji avtohtone, so: navadni glog (C. laevigata), enovrati glog (C. monogyna) ter čašasti glog (C. curvisepala). Poleg slovenskih avtohtonih vrst poznamo tudi tujerodne vrste. To so: ostrogasti glog (C. crus-galli), lavalejev glog (C. lavallei), slivolistni glog (C. persimilis) pensilvanski glog (C. pennsylvanica) idr. Rastišča se med vrstami zelo razlikujejo, kot se tudi njihove morfološke značilnosti. Skupno vsem vrstam gloga je, da vsebujejo fenolne spojine, terpenoide, vitamine, minerale ter tudi strupene snovi, to so cianogeni glikozidi. Zaradi zdravilnih snovi, ki jih vsebuje, se glog uporablja predvsem v zdravilne namene. Poleg tega ga uporabljajo tudi v kulinariki in lesarstvu. Za gojenje v Sloveniji priporočamo tiste vrste, ki dobro uspevajo v Sloveniji, torej navadni, enovrati in čašasti glog. Najboljše jih je gojiti v obliki vretenastega grma, pri tem pa naj bo sadilna razdalja v vrsti približno 3 metre, med vrstami pa približno 4 metre.The genus Crataegus about 250 plant species. The species of hawthorn that are autochthonous in Slovenia are: C. laevigata, C. monogyna and C. curvisepala. Besides Slovenian autochthonous species, we also know non-native species. These are C. crus-galli, C. lavallei, C. persimilis, C. pannsylvanica etc. Habitats vary greatly between species, as do their morphological characteristics. Common to all hawthorn species is that they contain phenolic compounds, terpenoids, vitamins, minerals and toxic compounds, such as cyanogenic glycosides. Due to the medicinal substances it contains, hawthorn is mainly used for medicinal purposes. In addition, it is also used in cooking and carpentry. For cultivation in Slovenia, we recommend those species that grow well in Slovenia, therefore C. laevigata, C. monogyna and C. curvisepala. It\u27s best that hawthorn is cultivated in a spindle-shaped form, with a planting distance of about 3 meters in a row and about 4 meters between rows

Negative effects of variable frequency drive utilization in marine electrical power system

Poznavanjem osnove elektromagnetizma, načine rada izmjeničnog asinkronog elektromotora i pretvarača frekvencije moguće je uočiti negativne posljedice korištenja istih u elektroenergetskom smislu; prema mreži i prema potrošaču. Prema mreži to su harmonična distorzija i utjecaj na ukupni faktor snage. Prema potrošaču, tj. elektromotoru to su izobličenja napona i ležajne struje. Shvaćanje ovih pojava i sposobnost umanjivanja negativnih posljedica korištenja pretvarača frekvencije ključni su za uspješno obavljanje poslova projektiranja i održavanja, tj. same eksploatacije današnjih brodskih elektroenergetskih sustava.By understanding the basics of electromagnetism, the working principles of both asynchronous electric motor and the variable frequency drive it is possible to understand the negative effects that originate from utilization of those devices in terms of electroenergetics. The effects toward the supply network are harmonic distortion and the effect on the total power factor. The second group are the effects towards the consumer, i.e. asynchronous electric motor; voltage distortion and bearing currents. The understanding of these phenomenons and the ability of mitigation the negative effects of variable frequency drive utilization is of vital importance for successful design, errection and maintenance, i.e. exploitation of todays electric power systems

Uloge epigenetskih modifikacija u embrionalnoj i adultnoj neurogenezi

The entire nervous system develops from common neural stem cells (NSCs) that line the neural tube during the first weeks of embryonic development. NSCs are self-renewing, multipotent cells that generate neural progenitor cells by asymmetric division, and which, through a limited number of divisions, differentiate into specialized cells of the nervous system: neurons, oligodendrocytes, and astrocytes. Although most neurons are generated before birth, it has been shown that under the influence of appropriate stimuli, in adult mammals and humans, neurogenesis continues throughout life in limited regions of the brain; the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone of the lateral ventricles. Generation of neurons from NSCs encompasses successive stages of progenitor expansion, differentiation, maturation, and integration of new-born neurons into functional neural circuits. Numerous intrinsic and extrinsic factors are involved in the regulation of neurogenesis, forming a complex network of signalling pathways. It seems that epigenetic modifications and their cooperation play an integral role in the precise control of gene expression, which is crucial for the proper acquisition of neural fate. This review will comprehensively summarize the hitherto known roles of epigenetic modifications, in particular DNA modifications, histone modifications and non-coding RNA molecules, in regulating both embryonic and adult neurogenesis in the vertebrate CNS, as well as their mutual mechanisms of cooperation. Further elucidation of the role of epigenetic mechanisms in the process of neurogenesis could lead to the development of novel therapies needed for the treatment of neurodevelopmental and neurodegenerative disorders.Čitav živčani sustav razvija se iz zajedničkih neuralnih matičnih stanica (eng. neural stem cells, NSCs) koje oblažu neuralnu cijev tijekom prvih tjedana embrionalnog razvoja. NSCs su samoobnavljajuće, multipotentne stanice koje asimetričnom diobom generiraju neuralne progenitorske stanice, a koje kroz ograničen broj dioba diferenciraju u specijalizirane stanice živčanog sustava: neurone, oligodendrocite i astrocite. Iako većina neurona nastaje prije rođenja, dokazano je da se pod utjecajem odgovarajućih podražaja, u odraslih sisavaca i čovjeka, neurogeneza nastavlja tijekom cijeloga života u ograničenim regijama mozga; subgranularnoj zoni dentatnog gyrus-a u hipokampusu i subventrikularnoj zoni bočnih ventrikula. Stvaranje neurona iz NSCs uključuje uzastopne faze ekspanzije progenitora, diferencijaciju, sazrijevanje i integraciju novih neurona u funkcionalne neuralne krugove. U regulaciji neurogeneze sudjeluju brojni unutarnji i vanjski čimbenici, tvoreći kompleksnu mrežu signalnih puteva. Čini se da upravo epigenetske modifikacije te njihova međusobna suradnja igra sastavnu ulogu u preciznoj kontroli genske ekspresije ključnoj za pravilno usmjeravanje NSCs u stjecanje neuralne sudbine. Ovaj pregledni rad sveobuhvatno će sažeti do sad poznate uloge epigenetskih modifikacija, točnije DNA modifikacija, histonskih modifikacija i nekodirajućih RNA molekula, u regulaciji embrionalne i odrasle neurogeneze u centralnom živčanom sustavu kralježnjaka, kao i njihove međusobne mehanizme suradnje. Daljnje rasvjetljivanje uloga epigenetskih mehanizama u procesu neurogeneze mogao bi dovesti do razvoja novih terapija za liječenje neurorazvojnih i neurodegenerativnih poremećaja

Negative effects of variable frequency drive utilization in marine electrical power system

Poznavanjem osnove elektromagnetizma, načine rada izmjeničnog asinkronog elektromotora i pretvarača frekvencije moguće je uočiti negativne posljedice korištenja istih u elektroenergetskom smislu; prema mreži i prema potrošaču. Prema mreži to su harmonična distorzija i utjecaj na ukupni faktor snage. Prema potrošaču, tj. elektromotoru to su izobličenja napona i ležajne struje. Shvaćanje ovih pojava i sposobnost umanjivanja negativnih posljedica korištenja pretvarača frekvencije ključni su za uspješno obavljanje poslova projektiranja i održavanja, tj. same eksploatacije današnjih brodskih elektroenergetskih sustava.By understanding the basics of electromagnetism, the working principles of both asynchronous electric motor and the variable frequency drive it is possible to understand the negative effects that originate from utilization of those devices in terms of electroenergetics. The effects toward the supply network are harmonic distortion and the effect on the total power factor. The second group are the effects towards the consumer, i.e. asynchronous electric motor; voltage distortion and bearing currents. The understanding of these phenomenons and the ability of mitigation the negative effects of variable frequency drive utilization is of vital importance for successful design, errection and maintenance, i.e. exploitation of todays electric power systems