The potential risk to humans from incidental ingestion of As-contaminated soil and mine waste is influenced by the mineralogical composition of the As phases present. Using the Solubility Bioaccessibility Research Consortium in vitro assay, simulating gastric conditions, we determined the oral bioaccessibility of As in 16 environmentally important As mineral(oid)s commonly found in mine waste and contaminated soils. Our results revealed a wide range of bioaccessibility values closely related to the solubility of the mineral(oid)s. Bioaccessibility values ranged from 0.15 % in minerals with great environmental stability such as scorodite and pharmacosiderite, to complete (100 %) release from minerals such as adamite, erythrite and pharmacolite. Intermediate bioaccessibility levels were observed in minerals such as arsenolite and yukonite, ranging from 6 % to 67 %. In mixtures with soil, the bioaccessibility of As in mineral(oid)s with low solubility was significantly reduced, with bioaccessibility values up to 8.7 times lower due to the effective adsorption of As by the soil. We conclude that the bioaccessibility of As in natural soil and mine waste is intricately influenced by both the mineralogical composition of As phases and the As retention capacity of natural materials under acidic conditions of gastric fluids.
- Klíčová slova
- Arsenic, Bioaccessibility, Mineral(oid)s, Soil, Solubility,
- MeSH
- arsen * analýza chemie MeSH
- biologická dostupnost * MeSH
- hornictví * MeSH
- látky znečišťující půdu * analýza chemie farmakokinetika MeSH
- lidé MeSH
- minerály * chemie MeSH
- rozpustnost * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- arsen * MeSH
- látky znečišťující půdu * MeSH
- minerály * MeSH
The hippocampus (HPC) is essential for navigation and memory, tracking environmental continuity and change, including navigation relative to moving targets. CA1 ensembles expressing immediate-early gene (IEG) Arc and Homer1a RNA are contextually specific. While IEG expression correlates with HPC-dependent task demands, the effects of behavioral demands on IEG-expressing ensembles remain unclear. In three experiments, we investigated the effects of context switch, sustained presence, and task demands on dorso-proximal CA1 IEG+ ensembles in rats. Experiment 1 showed that the size of IEG+ (Arc, Homer1a RNA) ensembles dropped to baseline during uninterrupted 30-min exploration, reflecting familiarization, unless a context switch was present. Context-specificity of the ensembles depended on both environment identity and timing of the context switch. Experiment 2 found no effect of HPC-dependent mobile robot avoidance or HPC-independent avoidance of a stationary robot on IEG+ ensembles beyond mere exploration. Experiment 3 replicated these findings for c-Fos protein. The data suggest that IEG+ ensembles are driven by a context switch and shrink over time during sustained presence in the same environment. We found no evidence of task demands or their change affecting the size, stability over time, or task-specificity of IEG+ ensembles. These results shed light on the temporal dynamics of CA1 IEG+ ensembles, and their control by contextual and behavioral factors.
- Klíčová slova
- Arc/Homer1a catFISH, Behavioral episode, C-Fos, Ensemble stability, Moving/stationary robot avoidance, RNA,
- MeSH
- chování zvířat fyziologie MeSH
- cytoskeletální proteiny genetika metabolismus MeSH
- hipokampální oblast CA1 * metabolismus fyziologie MeSH
- Homer scaffold proteiny * metabolismus genetika MeSH
- krysa rodu Rattus MeSH
- okamžité časné geny * fyziologie MeSH
- potkani Long-Evans * MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- activity regulated cytoskeletal-associated protein MeSH Prohlížeč
- cytoskeletální proteiny MeSH
- Homer scaffold proteiny * MeSH
- Homer1 protein, rat MeSH Prohlížeč
- proteiny nervové tkáně MeSH
The Huns appeared in Europe in the 370s, establishing an Empire that reshaped West Eurasian history. Yet until today their origins remain a matter of extensive debate. Traditional theories link them to the Xiongnu, the founders of the first nomadic empire of the Mongolian steppe. The Xiongnu empire dissolved, however, ~300 y before the Huns appeared in Europe, and there is little archaeological and historical evidence of Huns in the steppe during this time gap. Furthermore, despite the rich 5th to 6th centuries current era (CE) archaeological record of the Carpathian Basin, the cultural elements of connections with the steppe are limited to few findings and even fewer solitary eastern-type burials. In this study, we coanalyze archaeological evidence with 35 newly sequenced and published genomic data for a total of 370 individuals-from 5th to 6th century CE contexts in the Carpathian Basin including 10 Hun-period eastern-type burials, 2nd to 5th century sites across Central Asia and 2nd c. before current era (BCE) to 1st c. CE Xiongnu period sites across the Mongolian steppe. We find no evidence for the presence of a large eastern/steppe descent community among the Hun- and post-Hun-period Carpathian Basin population. We also observe a high genetic diversity among the eastern-type burials that recapitulates the variability observed across the Eurasian Steppe. This suggests a mixed origin of the incoming steppe conquerors. Nevertheless, long-shared genomic tracts provide compelling evidence of genetic lineages directly connecting some individuals of the highest Xiongnu-period elite with 5th to 6th century CE Carpathian Basin individuals, showing that some European Huns descended from them.
- Klíčová slova
- Huns, Middle Ages, Xiongnu, ancient DNA, trans-Eurasian mobility,
- MeSH
- archeologie * MeSH
- dějiny starověku MeSH
- genom lidský * MeSH
- lidé MeSH
- migrace lidstva dějiny MeSH
- starobylá DNA * analýza MeSH
- Check Tag
- dějiny starověku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- starobylá DNA * MeSH
Cellular senescence precipitates a decline in physiological activities and metabolic functions, often accompanied by heightened inflammatory responses, diminished immune function, and impaired tissue and organ performance. Despite extensive research, the mechanisms underpinning cellular senescence remain incompletely elucidated. Emerging evidence implicates circadian rhythm and hypoxia as pivotal factors in cellular senescence. Circadian proteins are central to the molecular mechanism governing circadian rhythm, which regulates homeostasis throughout the body. These proteins mediate responses to hypoxic stress and influence the progression of cellular senescence, with protein Brain and muscle arnt-like 1 (BMAL1 or Arntl) playing a prominent role. Hypoxia-inducible factor-1α (HIF-1α), a key regulator of oxygen homeostasis within the cellular microenvironment, orchestrates the transcription of genes involved in various physiological processes. HIF-1α not only impacts normal circadian rhythm functions but also can induce or inhibit cellular senescence. Notably, HIF-1α may aberrantly interact with BMAL1, forming the HIF-1α-BMAL1 heterodimer, which can instigate multiple physiological dysfunctions. This heterodimer is hypothesized to modulate cellular senescence by affecting the molecular mechanism of circadian rhythm and hypoxia signaling pathways. In this review, we elucidate the intricate relationships among circadian rhythm, hypoxia, and cellular senescence. We synthesize diverse evidence to discuss their underlying mechanisms and identify novel therapeutic targets to address cellular senescence. Additionally, we discuss current challenges and suggest potential directions for future research. This work aims to deepen our understanding of the interplay between circadian rhythm, hypoxia, and cellular senescence, ultimately facilitating the development of therapeutic strategies for aging and related diseases.
- Klíčová slova
- Cellular senescence, Circadian rhythm, Hypoxia, Potential therapy, Relationships,
- MeSH
- cílená molekulární terapie MeSH
- cirkadiánní rytmus * fyziologie MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus MeSH
- hypoxie buňky MeSH
- hypoxie metabolismus patofyziologie MeSH
- lidé MeSH
- signální transdukce MeSH
- stárnutí buněk * MeSH
- transkripční faktory ARNTL metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
- transkripční faktory ARNTL MeSH
Judges play a key role in the implementation of transitional justice mechanisms. Yet, less attention has been paid so far to the question of how to address their collaboration with non-democratic regimes. In theory, judges can be subjected to virtually all transitional justice mechanisms ranging from criminal prosecution and lustration to truth-seeking, or even amnesties. However, we show in a case study of Czechia that these mechanisms are not well equipped to address the complicity of judges in past crimes for three reasons: (1) judges usually play different roles in past crimes from political elites, (2) the principles of the separation of powers and judicial independence preclude the easy replacement of judges, and (3) pragmatic exigencies, such as the shortage of lawyers who are not tainted by cooperation with the previous regime, further complicate the renewal of the bench. Nevertheless, we argue that the lack of recognition of the role judges have played in non-democratic regimes is dangerous, as it may negatively affect public confidence in the judiciary and taint its legitimacy. Examples from Hungary, Poland and Romania, moreover, show that populist leaders are tempted to abuse the transitional justice rhetoric use the failure to deal with the past of judges as a justification for their court-curbing practices. Post-transition purges are therefore stuck between a rock (interfering in judicial independence and practical exigencies) and a hard place (mental dependence of the judiciary on the previous regime, low public trust in courts). When the democratic opposition defeats the populist leader, such as in Poland in 2023, it unfortunately faces the same dilemma. Thus, the Czech way of dealing with the past within the judiciary in transition from communism to democracy (transition 1.0) provides important insights also for today's undoing of populist judicial reforms and transition from authoritarian populism to democracy (transition 2.0).
- Klíčová slova
- Central and Eastern Europe, Judges, Judicial turnover, Judiciaries, Lustration, Purging, Removal of judges, Transitional justice,
- Publikační typ
- časopisecké články MeSH
MRE11 nuclease is a central player in signaling and processing DNA damage, and in resolving stalled replication forks. Here, we describe the identification and characterization of new MRE11 inhibitors MU147 and MU1409. Both compounds inhibit MRE11 nuclease more specifically and effectively than the relatively weak state-of-the-art inhibitor mirin. They also abrogate double-strand break repair mechanisms that rely on MRE11 nuclease activity, without impairing ATM activation. Inhibition of MRE11 also impairs nascent strand degradation of stalled replication forks and selectively affects BRCA2-deficient cells. Herein, we illustrate that our newly discovered compounds MU147 and MU1409 can be used as chemical probes to further explore the biological role of MRE11 and support the potential clinical relevance of pharmacological inhibition of this nuclease.
- Klíčová slova
- BRCA2, FEN1, MRE11 inhibitor, nuclease,
- MeSH
- homologní protein MRE11 * metabolismus antagonisté a inhibitory MeSH
- inhibitory enzymů * farmakologie chemie chemická syntéza MeSH
- lidé MeSH
- molekulární struktura MeSH
- objevování léků MeSH
- oprava DNA účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- homologní protein MRE11 * MeSH
- inhibitory enzymů * MeSH
- MRE11 protein, human MeSH Prohlížeč
Ormond's disease is a systemic autoimmune disease with serious complications. We present our retrospective analysis of 83 patients diagnosed with and treated for idiopathic retroperitoneal fibrosis (Ormond's disease) in our department from 1997 to 2023. In this retrospective study, we analysed the diagnostic approaches, the clinical history and surgical and immunosuppressive therapies, and their subsequent effects on our patients. Patients with established disease activity were given immunosuppressive treatment, using corticosteroids alone or in combination with azathioprine, in patients with exacerbation of the disease mycophenolate mofetil. Three patients with Ormond's disease and systemic complications (IgG4-related disease) were treated with rituximab. In the entire cohort, 83 patients received immunosuppressive therapy; the next 5 patients did not receive this treatment because they did not present inflammatory activity from the disease. In these 83 patients, computed tomography showed that immunosuppressive treatment resulted in partial or complete regression of the inflammatory infiltrate. Out of the 83 patients, 10 patients experienced disease exacerbation 7 and 24 months after the immunosuppressive treatment was discontinued. The follow-up ranged from 24 months to 26 years.
- Klíčová slova
- Hydronephrosis, Immunosuppression, Ormond’s disease, Periaortitis,
- MeSH
- dospělí MeSH
- imunosupresiva * terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- retroperitoneální fibróza * diagnóza farmakoterapie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- imunosupresiva * MeSH
Li-ion capacitors (LICs) integrate the desirable features of lithium-ion batteries (LIBs) and supercapacitors (SCs), but the kinetic imbalance between the both electrodes leads to inferior electrochemical performance. Thus, constructing an advanced anode with outstanding rate capability and terrific redox kinetics is crucial to LICs. Herein, heterostructured ZnS/SnS2 nanosheets encapsulated into N-doped carbon microcubes (ZnS/SnS2@NC) are successfully fabricated. The sufficient ZnS/SnS2 heterostructure possesses abundant active sites, and the built-in electric field formed at the heterojunction interface can facilitate electron/ion migration. The interconnected hollow carbon layers could reduce the electron transfer resistance effectively and accommodate the volume change of SnS2, thereby maintaining the structural stability. Due to the synergy between multi-components, the ZnS/SnS2@NC anode demonstrates impressive Li storage performance with an excellent cyclic durablity (690 mAh g-1 at 0.5 A g-1 after 600 cycles) and considerable rate capability. Moreover, when matched with active carbon, the ZnS/SnS2@NC based LIC device delivers an admirable energy density of 134.1 Wh kg-1 and a high power output of 11,250 W kg-1, as well as remarkable capacity retention of 73.2 % after 6,000 cycles at 1.0 A g-1. The experimental results demonstrate the significance of optimized heterointerface engineering toward construction of electrode materials with high-performance for Li storage.
- Klíčová slova
- Lithium-ion capacitors, carbon microcubes, electrochemical performance, heterostructure, metal sulfides,
- Publikační typ
- časopisecké články MeSH
The sternalis is an occasional muscle of the pectoral region with a reported incidence of around 7.8%. Higher rates of occurrences have been noted in females and in Asians. The muscle becomes clinically relevant as the muscle can be mis-interpreted as a pathological mass. Routine dissection was performed in a 68-year-old male and a 65-year-old female donated cadavers in the pectoral region. Gross anatomical features were meticulously noted, photographed and measurements were recorded with digital Vernier callipers. In the male cadaver, a long, slender, flat bi-tendinous sternalis was found, and in the female cadaver, tripartite sternalis possessing three distinct bellies was observed. Both the sternalis was right sided and were supplied by 2nd, 3rd and 4th intercostal nerves. Single bellied and tripartite sternalis are rare and they need to be recognized in the diagnostic images and during surgeries to avoid confusion.
- Klíčová slova
- Pectoral region, Sternalis, Sternalis muscle,
- MeSH
- kosterní svaly anatomie a histologie MeSH
- lidé MeSH
- mrtvola * MeSH
- prsní svaly MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
AIMS: To investigate the efficacy and safety of intravitreal Dexamethasone implant (DEX-I) therapy in the treatment of diabetic macular edema (DME) refractory to intravitreal bevacizumab (IVB). MATERIAL AND METHODS: This retrospective and cross-sectional study included 37 eyes of 37 patients who received 3 loading doses of IVB injections for DME with no response and underwent DEX-I implant. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurements and central foveal thickness (CFT) measured by spectral domain optical coherence tomography (SD-OCT) were recorded and compared before DEX-I, at the first week, first, second, third and sixth months. Duration of DME, glycated hemoglobin (HbA1c) levels, DME types and lens status (phakic, pseudophakic) were also recorded. RESULTS: The mean age of the patients was 61.14 ±8.69 years (59.5% male, 40.5% female). 35.1% of the patients had cystoid macular edema, 64.9% had diffuse macular edema and 73 % were phakic and 27% were pseudophakic. BCVA, CFT and IOP values before DEX-I injection were 0.78 ±0.16 LogMAR, 493.73 ±107.6 µm and 13.05 ±2.59 mmHg, respectively. At 6 months after DEX-I, BCVA, CFT and IOP values were 0.64 ±0.11 LogMAR, 397.35 ±59.72 µm and 16.3 ±2.51 mmHg, respectively. In all follow-ups, there was a significant improvement in BCVA, a significant decrease in CFT and a significant increase in IOP compared to pre-injection. Ocular hypertension was observed in 0.8 % of patients and progression of cataract progression in 1% of patients after treatment. CONCLUSION: DEX-I therapy is an effective and safe treatment option for DME refractory to IVB treatment.
- Klíčová slova
- Dexamethasone implant, bevacizumab, cataract, diabetic macular edema, intraocular pressure,
- MeSH
- bevacizumab aplikace a dávkování škodlivé účinky MeSH
- dexamethason * aplikace a dávkování škodlivé účinky MeSH
- diabetická retinopatie * farmakoterapie MeSH
- glukokortikoidy aplikace a dávkování škodlivé účinky MeSH
- injekce intravitreální * MeSH
- léky implantované * MeSH
- lidé středního věku MeSH
- lidé MeSH
- makulární edém * farmakoterapie etiologie diagnostické zobrazování MeSH
- průřezové studie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- zraková ostrost MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bevacizumab MeSH
- dexamethason * MeSH
- glukokortikoidy MeSH
- léky implantované * MeSH
