Current studies reveal that the biomineralization of U(VI) by anaerobes normally produces nano-sized U(IV) minerals that can easily re-migrate/re-oxidize, while the biomineralization of U(VI) by aerobes has been constrained because the general mechanism has not yet been fully characterized. The biomineralization of U(VI) by Bacillus cereus 12-2 was investigated in this work. The maximum biosorption capability of intact cells was 448.68 mg U/g biomass (dry weight) at pH 5, while a decrease over 60% was induced when phosphate, amino, and especially carboxyl groups were shielded. X-ray diffraction, electron microscopy, and tracing the concentration of soluble intracellular U(VI) demonstrated that extracellular amorphous uranium particles can directly enter cells as solid, and about 10 nm-sized (NH4)(UO2)PO4·3H2O was formed subsequently. It was also revealed that the biosorption capability was not affected by a high uranium concentration, while biomineralization was inhibited, suggesting that a high concentration of heavy metals may inhibit the enzyme activity involved in biomineralization. Besides, U(VI) could trigger the overexpression of proteins with a molecular weight of 22 kD, including various phosphatases, kinases, and other enzymes that are related to metabolism and stimulus response, which may contribute to the intracellular transformation of U(VI) compounds from amorphous to crystalline phase. Taken together, the immobilization of U(VI) by B. cereus 12-2 contains two major steps: (1) fast immobilization of U(VI) on the cell surface as amorphous compounds, in which the carboxyl groups served as the predominant coordination functional groups and (2) transport of amorphous particles to cells directly and enzyme-related formation of uramphite.

• MeSH
• Bacillus cereus chemie   MeSH
• difrakce rentgenového záření metody   MeSH
• minerály chemie   MeSH
• uran chemie   MeSH
• Publikační typ
• časopisecké články MeSH

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

• MeSH
• antibakteriální látky terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• Helicobacter pylori * účinky léků   MeSH
• infekce vyvolané Helicobacter pylori * farmakoterapie   epidemiologie   mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metronidazol terapeutické užití   aplikace a dávkování   MeSH
• nádory žaludku * prevence a kontrola   epidemiologie   mikrobiologie   MeSH
• omeprazol * terapeutické užití   aplikace a dávkování   MeSH
• organokovové sloučeniny terapeutické užití   aplikace a dávkování   MeSH
• senioři MeSH
• tetracyklin terapeutické užití   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Čína MeSH

Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals.

• MeSH
• alely MeSH
• chov zvířat metody   MeSH
• chov MeSH
• destičkový růstový faktor metabolismus   MeSH
• divoká zvířata genetika   MeSH
• druhová specificita MeSH
• fenotyp MeSH
• frekvence genu MeSH
• genetická variace MeSH
• genetika MeSH
• genomika MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• mutace MeSH
• ovce domácí genetika   MeSH
• ovce MeSH
• sekvenční analýza DNA MeSH
• sekvenování celého genomu MeSH
• selekce (genetika) MeSH
• vazebná nerovnováha MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Pancreatic ductal adenocarcinoma (PDAC), the most deadly solid malignancy, is typically detected late and at an inoperable stage. Early or incidental detection is associated with prolonged survival, but screening asymptomatic individuals for PDAC using a single test remains unfeasible due to the low prevalence and potential harms of false positives. Non-contrast computed tomography (CT), routinely performed for clinical indications, offers the potential for large-scale screening, however, identification of PDAC using non-contrast CT has long been considered impossible. Here, we develop a deep learning approach, pancreatic cancer detection with artificial intelligence (PANDA), that can detect and classify pancreatic lesions with high accuracy via non-contrast CT. PANDA is trained on a dataset of 3,208 patients from a single center. PANDA achieves an area under the receiver operating characteristic curve (AUC) of 0.986-0.996 for lesion detection in a multicenter validation involving 6,239 patients across 10 centers, outperforms the mean radiologist performance by 34.1% in sensitivity and 6.3% in specificity for PDAC identification, and achieves a sensitivity of 92.9% and specificity of 99.9% for lesion detection in a real-world multi-scenario validation consisting of 20,530 consecutive patients. Notably, PANDA utilized with non-contrast CT shows non-inferiority to radiology reports (using contrast-enhanced CT) in the differentiation of common pancreatic lesion subtypes. PANDA could potentially serve as a new tool for large-scale pancreatic cancer screening.

• MeSH
• deep learning * MeSH
• duktální karcinom slinivky břišní * diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• nádory slinivky břišní * diagnostické zobrazování   patologie   MeSH
• pankreas diagnostické zobrazování   patologie   MeSH
• počítačová rentgenová tomografie MeSH
• retrospektivní studie MeSH
• umělá inteligence MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667-248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.

• MeSH
• biologická adaptace genetika   MeSH
• biologická evoluce MeSH
• fylogeografie MeSH
• genetická variace MeSH
• genová introgrese * MeSH
• klimatické změny MeSH
• odolnost vůči nemocem genetika   MeSH
• ovce genetika   imunologie   MeSH
• pneumonie imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Resistance to glucocorticoids (GC), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-offunction experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GC-resistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GC against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

• MeSH
• antigeny CD9 * metabolismus   genetika   MeSH
• chemorezistence * genetika   MeSH
• dexamethason farmakologie   MeSH
• dítě MeSH
• glukokortikoidy * farmakologie   terapeutické užití   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• pre-B-buněčná leukemie * farmakoterapie   metabolismus   genetika   patologie   MeSH
• předškolní dítě MeSH
• receptory glukokortikoidů metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.

• MeSH
• adenokarcinom genetika   MeSH
• běloši genetika   MeSH
• celogenomová asociační studie * MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• homeostáza telomer genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• kouření epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokus kvantitativního znaku MeSH
• mapování chromozomů MeSH
• nádory plic epidemiologie   etnologie   genetika   MeSH
• senioři MeSH
• zdraví rodiny MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

• MeSH
• autofagie * fyziologie   MeSH
• biotest metody   normy   MeSH
• lidé MeSH
• počítačová simulace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• směrnice MeSH

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

• MeSH
• autofagie * fyziologie   MeSH
• autofagozomy MeSH
• biologické markery MeSH
• biotest normy   MeSH
• lidé MeSH
• lyzozomy MeSH
• proteiny spojené s autofagií metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• směrnice MeSH

• MeSH
• chirurgie trávicího traktu metody   MeSH
• nemoci trávicího systému chirurgie   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• chirurgie
• NLK Publikační typ
• kolektivní monografie