Chromatin ‘readers’ are central interpreters of the epigenome that facilitate cell-specific transcriptional programs and are therapeutic targets in cancer and inflammation. The Speckled Protein (SP) ...family of chromatin ‘readers’ in humans consists of SP100, SP110, SP140, and SP140L. SPs possess functional domains (SAND, PHD, bromodomain) that dock to DNA or post-translationally modified histones and a caspase activation and recruitment domain (CARD) to promote multimerization. Mutations within immune expressed SPs associate with numerous immunological diseases including Crohn’s disease, multiple sclerosis, chronic lymphocytic leukemia, veno-occlusive disease with immunodeficiency, as well as Mycobacterium tuberculosis infection, underscoring their importance in immune regulation. In this review, we posit that SPs are central chromatin regulators of gene silencing that establish immune cell identity and function.
The speckled protein (SP) family of chromatin ‘readers’ in humans comprises SP100, SP110, SP140, and SP140L.The mouse SP family comprises Sp100, Sp110, and Sp140 and is only ~45% homologous to human SPs at the amino acid level, necessitating both mouse and human studies of SPs.SPs are highly expressed in innate and adaptive immune cells, with SP140 being immune restricted. SPs are also interferon (IFN)-stimulated genes (ISGs).Mutations in human SP140 associate with three immunological diseases: Crohn’s disease, chronic lymphocytic leukemia, and multiple sclerosis. Mutations in human SP110 associate with veno-occlusive disease with immunodeficiency (VODI). Mouse SPs can act as determinants of resistance to intracellular pathogen infections such as Mycobacterium tuberculosis.The SP family members possess a SAND domain, a plant homeodomain (PHD), and a caspase activation and recruitment domain (CARD) that share high homology with these domains found in autoimmune regulator (Aire); these domains suggest that SPs can bind to DNA directly, ‘read’ histone methylation status, and multimerize, respectively. In addition, SPs contain a bromodomain (BRD) that may read histone acetylation status.Human SPs localize to promyelocytic leukemia (PML) nuclear bodies (NBs) in human cell lines – dynamic nuclear protein aggregates interspersed between chromatin that can measure up to 2 μm in diameter. The presence of an intrinsically disordered region (IDR) exclusively in human SPs suggest that they may phase separate.By virtue of their localization to PML-NBs, SPs have been implicated in transcriptional repression of host or viral genomes. The function of SP140 was recently elucidated showing that it occupies heterochromatin and represses lineage-inappropriate genes such as HOX to maintain macrophage identity in mice and humans.
Heavy-metal pollution (such as Cd(II)) is regarded as a serious environmental problem, posing a great threat to human beings. In this research, a novel water-dispersible magnetic ...alginate/hydroxyapatite composite with high-efficiency Cd(II) adsorption performance was successfully synthesized by a facile wet-chemical method. The magnetic separation experiment and magnetic property analysis indicate that a magnetic alginate/hydroxyapatite composite can be effectively separated under a magnetic field. The zeta-potential result and dispersity experiment indicate that the lowest zeta-potential is –39.4 mV at pH = 5, and the obtained sample dispersed well in a Cd(II) solution after 120 min. The maximum adsorption capacity of a sample on Cd(II) is 135.3 mg g–1 at pH = 5, and the adsorption of Cd(II) reached equilibrium in 10 min. The adsorption data could be fitted well using the Langmuir model, and the adsorption kinetic follows a pseudo-second-order kinetic model.
Mutations in Sp110 are the underlying cause of veno-occlusive disease with immunodeficiency (VODI), a combined immunodeficiency that is difficult to treat and often fatal. Because early treatment is ...critically important for patients with VODI, broadly usable diagnostic tools are needed to detect Sp110 protein deficiency. Several factors make establishing the diagnosis of VODI challenging: (1) Current screening strategies to identify severe combined immunodeficiency are based on measuring T cell receptor excision circles (TREC). This approach will fail to identify VODI patients because the disease is not associated with severe T cell lymphopenia at birth; (2) the
SP110
gene contains 17 exons, making it a challenge for Sanger sequencing. The recently developed next-generation sequencing (NGS) platforms that can rapidly determine the sequence of all 17 exons are available in only a few laboratories; (3) there is no standard functional assay to test for the effects of novel mutations in Sp110; and (4) it has been difficult to use flow cytometry to identify patients who lack Sp110 because of the low level of Sp110 protein in peripheral blood lymphocytes. We report here a novel flow cytometric assay that is easily performed in diagnostic laboratories and might thus become a standard assay for the evaluation of patients who may have VODI. In addition, the assay will facilitate investigations directed at understanding the function of Sp110.
Abstract Familial hepatic veno-occlusive disease with immunodeficiency (VODI, OMIM: 235550 ), a rare form of severe combined immune deficiency, was first described in Australian Lebanese patients as ...being associated with homozygous mutations in SP110 , a gene encoding a PML nuclear body-associated protein. We present the first case of confirmed VODI in the United States, and identify the first novel missense mutation in SP110. The 3-year-old daughter of Hispanic parents without known consanguinity presented at age 5 months with fever, hepatomegaly, and pancytopenia. Her brother died at age 3 months from hepatic failure of undetermined etiology. Initial T- and B-cell counts were low, but eventually normalized. Serum IgG and IgM levels were low for age. Lymphoproliferation to mitogens and allogenic B-cells was normal, but absent to tetanus and candida antigens. Serum antibody levels against pneumococcal, Hib and tetanus antigens were low. Liver biopsies at ages 5 and 9 months were consistent with hepatic veno-occlusive disease or hVOD (also known as sinusoidal obstruction syndrome or SOS) and broncho-alveolar lavage detected Pneumocystis jiroveci . The patient recovered from her acute disease and has been clinically stable on immunoglobulin replacement therapy and trimethoprim-sulfamethoxazole prophylaxis. T-Cell receptor excision circle (TREC) analysis suggests that VODI will not be detected by newborn screening for severe combined immunodeficiency that relies on this assay. DNA was obtained from the patient, 4 siblings, and both parents, and SP110 was sequenced. The first missense mutation, a homozygous deletion/insertion variation in exon 2 ( NM_080424.2 (SP110):c.78_79delinsAT) was detected in the patient. This novel mutation segregated in the heterozygous state in other living unaffected family members. The mechanism by which this SP110 mutation associates with VODI is consistent with the normal length mutated SP110 protein being subject to enhanced proteosome degradation resulting in marked reductions in SP110 protein.
U ovome preglednom radu dan je uvid u život i rad doajena znanosti o zračenju i zaštite od zračenja u Hrvatskoj do 1945. godine. Efektivni počeci znanosti o zračenju, pa tako i zaštite od zračenja na ...području Hrvatske sežu čak do kraja 19. stoljeća. Fizičari i kemičari bili su među prvima mogućim žrtvama izloženosti ionizirajućem zračenju, pa su tako i bili prvi koji su upozoravali na štetne učinke radijacije na žive organizme.
Pretraživanje dostupnih arhiva i poznate literature nije samo rasvijetlilo život i rad doajena znanosti o zračenju već je omogućilo sistematičan uvid u do sada nepoznate detalje važne za povijest i razvoj znanosti o zračenju, zaštite od zračenja, kao i o medicinskoj fi zici. Sve to pokazuje da Hrvatska od samoga početka ne samo da slijedi najsuvremenije znanstvene spoznaje iz tih područja, već i njima aktivno pridonosi.
Projekt »Green Hull Duca, Giuseppe; d’Alberton, Paola; Grbec, Mitja
Poredbeno pomorsko pravo,
12/2022, Volume:
61, Issue:
176
Paper
Open access
»Green Hull« je projekt koji se provodi uz potporu Programa suradnje Interreg V-A, Italija-Slovenija, a financira ga Europski fond za regionalni razvoj. Usmjeren je na rješavanje problema onečišćenja ...okoliša uzrokovanog biološkim naslagama na trupovima brodova. Trupovi se brodova čiste dok su još u morskoj vodi, bez izlijevanja zagađujućih ili opasnih tvari. Na taj se način poboljšavaju performanse brodova i smanjuje unošenje alohtonih vrsta u okoliš, bez troškova i vremena potrebnog za suhi dok. More ne poznaje granice; nužna je prekogranična suradnja u javnom i privatnom sektoru kako bi se definirale smjernice za kontrolu, praćenje i gospodarenje vodom i otpadom od bioloških naslaga na trupovima brodova te kako bi se osiguralo učinkovitije prekogranično upravljanje tim rizikom. U sklopu projekta »Green Hull« istraživala se zakonska regulativa koja se odnosi na zaštitu okoliša i kvalitetu morskih voda, na međunarodnoj, europskoj te nacionalnoj razini, što se tiče talijanskog i slovenskog zakonodavstva. Studija pravnih aspekata projektnog područja također je bila usmjerena na pripremu, u okviru postojeće regulative, smjernica za razvoj zelenih tehnologija u sektoru od interesa za projekt, te model sustava za gospodarenje otpadom koji nastaje čišćenjem brodova.
Hidrokineziterapija se koristi u liječenju različitih bolesti i stanja, ali i za poboljšanje fizioloških perfor-mansi mišićno-koštanog sustava. Voda predstavlja idealan medij kojim se mogu postići ...različiti rehabi-litacijski ili trenažni ciljevi, kombinirajući različite učinke njenih fizikalnih i kemijskih svojstava. Hidro-kineziterapija u termomineralnoj vodi može pojačati učinke imerzijske hidroterapije, ali je potreban o-prez s obzirom na kardiorespiratorni status pojedinca. Cilj ovog rada je prikazati učinke hidrokinezite-rapije u različitim rehabilitacijskim i trenažnim programima s posebnim osvrtom na učinak u termomine-ralnoj vodi, naglasiti njezine korisne, ali i ograničavajuće učinke.
U ovome preglednom radu dan je uvid u život i rad doajena znanosti o zračenju i zaštite od zračenja u Hrvatskoj do 1945. godine. Efektivni počeci znanosti o zračenju, pa tako i zaštite od zračenja na ...području Hrvatske sežu čak do kraja 19. stoljeća. Fizičari i kemičari bili su među prvima mogućim žrtvama izloženosti ionizirajućem zračenju, pa su tako i bili prvi koji su upozoravali na štetne učinke radijacije na žive organizme. Pretraživanje dostupnih arhiva i poznate literature nije samo rasvijetlilo život i rad doajena znanosti o zračenju već je omogućilo sistematičan uvid u do sada nepoznate detalje važne za povijest i razvoj znanosti o zračenju, zaštite od zračenja, kao i o medicinskoj fizici. Sve to pokazuje da Hrvatska od samoga početka ne samo da slijedi najsuvremenije znanstvene spoznaje iz tih područja, već i njima aktivno pridonosi.
Physicists and chemists were among the first potential victims of occupational exposure to ionising radiation and they were also the first to warn about the harmful effects of radiation on living organisms. This review presents the work of the first notable scientists in the field of radiation science in Croatia from the discovery of radiation (Henry Becquerel in 1896) to 1945. The beginning of radiation science and radiation protection in Croatia can be traced to the end of the 19th century. Our research of the archived material and literature not only gave a deeper insight to the life and work of some of these notable scientists, but also gave a glimpse of previously unknown facts and details important for the history and development of radiation science, radiation protection, as well as medical physics. Our research has shown that Croatian scientists not only kept pace with contemporary scientific knowledge but also made notable contributions from the very beginning.
Pozadina istraživanja. Karcinom dojke jedan je od najčešćih tipova tumora te je još uvijek glavni uzročnik morbiditeta i mortaliteta među ženama diljem svijeta. U razvijenim zemljama ova ...multifaktorska bolest predstavlja primarni zdravstveni problem, a u stalnom je porastu u srednje i nisko razvijenim zemljama. Mnoga istraživanja pokazuju da fitokemikalije poput karotenoida suzbijaju rast i potiču apoptozu stanica karcinoma dojke. Nedavno smo poboljšali topljivost kapsantina u vodi postupkom inkapsulacije u novom neionskom surfaktantu, diosgenin polietilenglikol sukcinatu. Stoga je svrha ovoga rada bila pomoću MTT testa ispitati in vitro citotoksičnost micela punjenih kapsantinom, topljivih u vodi, na stanice raka MDA-MB-231.
Eksperimentalni pristup. U radu je iz ekstrakta slatke crvene paprike (Capsicum annuum) izoliran hidrofobni karotenoid kapsantin. Iz čvrste disperzije ekstrakta i diosgenin polietilenglikol sukcinata 1000 pripremljene su micele. Ekstrakt kapsantina i micele su okarakterizirani pomoću UV-Vis spektroskopije, visokodjelotvorne tekućinske kromatografije, infracrvene spektroskopije s Fourierovom transformacijom, difrakcije X-zraka, raspodjele veličine čestica, polidisperzije i pretražne elektronske mikroskopije. Ispitali smo učinak ekstrakta kapsantina i micela na preživljavanje i rast trostruko negativnih stanica raka dojke (MDA-MB-231) te citotoksičnost micela.
Rezultati i zaključci. Bitno se povećala topljivost kapsantina u inkapsuliranim micelama i time proširila mogućnost njegove primjene za ciljanu isporuku, čime se postižu bolji rezultati u liječenju rezidualnih tumora. Inkapsulirani se kapsantin kontrolirano otpuštao pri simulaciji probave u crijevima (pH=6,8). Predloženi sustav za ciljanu isporuku lijeka s produljenim djelovanjem omogućuje učinkovito i kontrolirano otpuštanje aktivne tvari na mjestu djelovanja. Rezultati pokazuju da se pri inkapsulaciji kapsantina nije promijenila njegova struktura, a niti sastav funkcionalnih skupina. Citotoksičnost micela na stanice MDA-MB-231 (IC50=(3,10±1,09) μg/mL) bila je bitno veća od one ekstrakta kapsantina (IC50=(81,1±1,5) μg/mL). Ekstrakt kapsantina i micele s kapsantinom mogu se upotrijebiti za poticanje apoptoze i povećanje količine reaktivnih kisikovih spojeva u stanicama raka.
Novina i znanstveni doprinos. Rezultati prvi put prikazuju citotoksični učinak kapsantina i micela s kapsantinom na stanice raka MDA-MB-231. Kapsantin izoliran iz slatke crvene paprike (Capsicum annuum) imao je izniman citotoksični učinak na trostruko negativne stanice raka MDA-MB-231.
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