ABSTRACT
This article reports quasi-continuous transiting events towards WD 1054–226 at d = 36.2 pc and V = 16.0 mag, based on simultaneous, high-cadence, multiwavelength imaging photometry using ...ULTRACAM over 18 nights from 2019 to 2020 March. The predominant period is 25.02 h and corresponds to a circular orbit with blackbody Teq = 323 K, where a planetary surface can nominally support liquid water. The light curves reveal remarkable night-to-night similarity, with changes on longer time-scales, and lack any transit-free segments of unocculted starlight. The most pronounced dimming components occur every 23.1 min – exactly the 65th harmonic of the fundamental period – with depths of up to several per cent, and no evident colour dependence. Myriad additional harmonics are present, as well as at least two transiting features with independent periods. High-resolution optical spectra are consistent with stable, photospheric absorption by multiple, refractory metal species, with no indication of circumstellar gas. Spitzer observations demonstrate a lack of detectable dust emission, suggesting that the otherwise hidden circumstellar disc orbiting WD 1054–226 may be typical of polluted white dwarfs, and detected only via favourable geometry. Future observations are required to constrain the orbital eccentricity, but even if periastron is near the Roche limit, sublimation cannot drive mass loss in refractory parent bodies, and collisional disintegration is necessary for dust production.
This randomized, controlled trial involving patients with complicated intraabdominal infections and proper source control showed similar outcomes after fixed-duration antimicrobial therapy (4 days) ...and after a longer course (approximately 8 days).
Complicated intraabdominal infection continues to be a common problem worldwide. Approximately 300,000 cases of appendicitis occur each year in the United States,
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and at least twice that many cases of non-appendiceal infection require management.
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Morbidity ranges from 5% among patients evaluated in broad observational studies
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–
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to close to 50% in some cohorts, such as the elderly or critically ill.
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Despite the diversity of specific processes in these infections, the basic tenets of management are similar: resuscitate patients who have the systemic inflammatory response syndrome (SIRS), control the source of contamination, remove most of the infected or necrotic material, . . .
Staphylococcus aureus is a frequent cause of mastitis in dairy cows. However, pathogenesis of the infection has not been completely defined. We report the invasion of two strains of S. aureus into a ...bovine mammary epithelial cell line and a bovine mammary epithelial cell primary culture. Invasion of S. aureus into bovine mammary cells was time-dependent. Transmission electron microscopy of bovine mammary cells invaded by S. aureus showed intracellular replication of the bacterium within membrane-bound vacuoles. Invasion was reduced significantly when bovine mammary epithelial cells were treated with inhibitors of F-actin microfilament polymerization but not when these cells were treated with inhibitors of microtubule formation. Results indicated that S. aureus is capable of invading and replicating inside bovine mammary epithelial cells. Data also suggested that S. aureus invasion of bovine mammary epithelial cells requires active participation of specific components of the cytoskeleton of the epithelial cell.
Neuroblastoma is a paediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumours with ...excellent outcomes to widely metastatic disease in which long-term survival is approximately 40% despite intensive therapy. A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumour cells. Here we investigate the causal DNA variant at this locus and the mechanism by which it leads to neuroblastoma tumorigenesis. We first imputed all possible genotypes across the LMO1 locus and then mapped highly associated single nucleotide polymorphism (SNPs) to areas of chromatin accessibility, evolutionary conservation and transcription factor binding sites. We show that SNP rs2168101 G>T is the most highly associated variant (combined P = 7.47 × 10(-29), odds ratio 0.65, 95% confidence interval 0.60-0.70), and resides in a super-enhancer defined by extensive acetylation of histone H3 lysine 27 within the first intron of LMO1. The ancestral G allele that is associated with tumour formation resides in a conserved GATA transcription factor binding motif. We show that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (P = 0.028) in neuroblastoma primary tumours, and ablates GATA3 binding (P < 0.0001). We demonstrate allelic imbalance favouring the G-containing strand in tumours heterozygous for this SNP, as demonstrated both by RNA sequencing (P < 0.0001) and reporter assays (P = 0.002). These findings indicate that a recently evolved polymorphism within a super-enhancer element in the first intron of LMO1 influences neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumour cells.
•Epidemiological evidence has identified several viral cofactors in HPV-associated cervical and oral carcinomas.•A common feature of viral cofactors in HPV-associated carcinoma is their ability to ...establish lifelong persistent infections.•Viral cofactors in HPV-associated cancer may act through direct infection of tumor cells or indirectly through various mechanisms.
The etiological role of human papillomavirus (HPV) in anogenital tract and head and neck cancers is well established. However, only a low percentage of HPV-positive women develop cancer, indicating that HPV is necessary but not sufficient in carcinogenesis. Several biological and environmental cofactors have been implicated in the development of HPV-associated carcinoma that include immune status, hormonal changes, parity, dietary habits, tobacco usage, and co-infection with other sexually transmissible agents. Such cofactors likely contribute to HPV persistent infection through diverse mechanisms related to immune control, efficiency of HPV infection, and influences on tumor initiation and progression. Conversely, HPV co-infection with other factors may also harbor anti-tumor effects. Here, we review epidemiological and experimental studies investigating human immunodeficiency virus (HIV), herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), BK virus (BKV), JC virus (JCV), and adeno-associated virus (AAV) as viral cofactors in or therapeutic factors against the development of genital and oral HPV-associated carcinomas.
People's risk perception of COVID-19 is an important predictor for adopting protective behavior. Although risk perceptions, and factors influencing these, may vary between countries, less attention ...has been paid to differences between adjacent regions from neighboring countries. In the midst of the first wave of the corona outbreak (March-April-May 2020), we measured risk perceptions as perceived threat (consisting of perceived severity and susceptibility) among university students (N = 668) in two connected countries: the Netherlands and Belgium. Theory-based predictor variables included experiential, efficacy-related, socio-cultural, cognitive, and demographic factors. While demographic variables and country were not significant predictors of perceived threat level, all other constructs were. Personal and indirect experiences with COVID-19, as well as higher scores on personal (self) efficacy to carry out recommended preventive behaviors were all associated with higher perceived threat. However, low collective efficacy and lower levels of trust in government were both also significantly associated with higher perceived threat, as was a low level of "lack of COVID-19 knowledge". These results hold implications for suitable risk communication strategies for increasing students' COVID-19 risk perceptions.
A preceding paper by Guidry et al 2013 Comput. Sci. Disc. 6 015001 demonstrated that explicit asymptotic methods generally work much better for extremely stiff reaction networks than has previously ...been shown in the literature. There we showed that for systems well removed from equilibrium, explicit asymptotic methods can rival standard implicit codes in speed and accuracy for solving extremely stiff differential equations. In this paper, we continue the investigation of systems well removed from equilibrium by examining quasi-steady-state (QSS) methods as an alternative to asymptotic methods. We show that for systems well removed from equilibrium, QSS methods also can compete with, or even exceed, standard implicit methods in speed, even for extremely stiff networks, and in many cases give a somewhat better integration speed than for asymptotic methods. As for asymptotic methods, we will find that QSS methods give correct results, but with a non-competitive integration speed as equilibrium is approached. Thus, we find that both asymptotic and QSS methods must be supplemented with partial equilibrium methods as equilibrium is approached to remain competitive with implicit methods.
We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition ...to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and MIRLET7A loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development.
Repetitive administration of phencyclidine (PCP) in the perinatal period results in cortical apoptosis and a long-lasting deficit in sensorimotor gating. Because these changes are ...olanzapine-sensitive, we have suggested that the effects of perinatal PCP could be used to model certain aspects of schizophrenia. Studies of PCP and N-methyl-D-aspartate-induced cell death suggested that superoxide could play a role in the pathway leading to death after PCP administration. The purpose of the current study was to determine whether the in vivo administration of M40403, a superoxide dismutase mimetic, could prevent PCP-induced cortical apoptosis and/or deficits in prepulse inhibition. Perinatal rat pups were administered 10 mg/kg PCP on postnatal (PN) days 7, 9, and 11 with or without treatment with 10 mg/kg M40403. Pups were either killed on PN 12 for analysis of various apoptotic markers or they were assessed for prepulse inhibition on PN 24 to 26. Treatment with M40403 2 and 24 h after each PCP treatment prevented PCP-induced increases in two measures of apoptosis in the dorsolateral frontal cortex and in the olfactory cortex. PCP-induced proapoptotic changes in Bax and Bcl-X(L) were also prevented by M40403 treatment. This regimen did not prevent the deficit in prepulse inhibition caused by PCP treatment, but when the treatment regimen was extended through PN 23, M40403 completely prevented the PCP-induced deficit in prepulse inhibition. These data suggest that perinatal PCP treatment leads to long-lasting changes in the pathway(s), leading to cell death and behavioral deficits, and that the superoxide radical plays a critical role in the underlying mechanism.
Screening for human papillomavirus (HPV) integration into host cell chromosomes typically requires large amounts of time and reagents. We developed a rapid and sensitive assay based on exonuclease V ...(ExoV) and quantitative polymerase chain reaction (qPCR) to determine HPV genome configurations in cell lines and tissues. We established the assay using genomic DNA from cell lines known to harbor integrated or episomal HPV16. DNA was incubated with ExoV, which is specific for linear DNA, and the DNA fraction resistant to digestion was measured by qPCR. The percent of DNA resistant to ExoV digestion was calculated relative to undigested DNA for determination of episomal or integrated HPV16. The ExoV assay was accurate, capable of distinguishing episomal from integrated HPV16 in cell lines and tissues. Future applications of the ExoV assay may include screening of HPV genome configurations in the progression of HPV-associated cancers.
•The ExoV assay is rapid and sensitive in detecting episomal and integrated HPV DNA.•The ExoV assay with HPV copy number identified episomal from type 1 or 2 integrants.•The ExoV assay monitors the physical state of HPV16 in organotypic raft tissues.
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