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Btn2p/Cur1p overproduction cures [URE3] variants with low seed number, but seed number is not increased in rpl4aΔ, rpl21bΔ or ubr2Δ mutants. Knockouts of genes required for the protein sorting function of Btn2p did not affect curing of [URE3], nor did inactivation of the Hsp104 prion-curing activity. Overactivity of the ubiquitin/proteasome system, resulting from 60S subunit deficiency or ubr2Δ, may impair Cur1p and Btn2p curing of [URE3] by degrading Cur1p, Btn2p or another component of these curing systems.Gln3 activates Nitrogen Catabolite Repression, NCR-sensitive expression of the genes required for Saccharomyces cerevisiae to scavenge poor nitrogen sources from its environment. The global TorC1 kinase complex negatively regulates nuclear Gln3 localization, interacting with an α-helix in the C-terminal region of Gln3, Gln3656-666. In nitrogen replete conditions, Gln3 is sequestered in the cytoplasm, whereas when TorC1 is down-regulated, in nitrogen restrictive conditions, Gln3 migrates into the nucleus. In this work, we show that the C-terminal Gln3-Tor1 interaction site is required for wild type, rapamycin-elicited, Sit4-dependent nuclear Gln3 localization, but not for its dephosphorylation. In fact, truncated Gln31-384 can enter the nucleus in the absence of Sit4 in both repressive and derepressive growth conditions. However, Gln31-384 can only enter the nucleus if a newly discovered second positively-acting Gln3-Tor1 interaction site remains intact. Importantly, the N- and C-terminal Gln3-Tor1 interaction sites function both autonomously and collaboratively. The N-terminal Gln3-Tor1 interaction site, previously designated Gln3URS contains a predicted α-helix situated within an unstructured coiled-coil region. Eight of the thirteen serine/threonine residues in the Gln3URS are dephosphorylated 3-15-fold with three of them by 10-15-fold. Substituting phosphomimetic aspartate for serine/threonine residues in the Gln3 URS abolishes the N-terminal Gln3-Tor1 interaction, rapamycin-elicited nuclear Gln3 localization, and ½ of the derepressed levels of nuclear Gln3 localization. Cytoplasmic Gln3 sequestration in repressive conditions, however, remains intact. These findings further deconvolve the mechanisms that achieve nitrogen-responsive transcription factor regulation downstream of TorC1.
Healthcare personnel (HCP) are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We posit current infection control guidelines generally protect HCP from SARS-CoV-2 infection in a healthcare setting.
In this retrospective case series, we use viral genomics to investigate the likely source of SARS-CoV-2 infection in HCP at a major academic medical institution in the Upper Midwest of the United States between 25 March - 27 December, 2020. We obtain limited epidemiological data through informal interviews and review of the electronic health record. We combine epidemiological information with healthcare-associated viral sequences and with viral sequences collected in the broader community to infer the most likely source of infection in HCP.
We investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. The majority of HCP infections could not be linked to a patient or co-worker (55/95; 57.9%) and were genetically simyptic healthcare-associated transmission, it appears that HCP most commonly becomes infected with SARS-CoV-2 via community exposure. This emphasizes the ongoing importance of mask-wearing, physical distancing, robust testing programs, and rapid distribution of vaccines.We describe the prevalence of Pneumocystis jirovecii in mother-infant pairs of very low birth weight newborns less then 32 weeks gestation. Molecular and microscopic methods were used for detection of P. jirovecii in patients' specimens. Pneumocystis DNA was detected in eight nasopharyngeal aspirates (14%) of 56 newborns and in seven oral washes (21%) of 34 mothers. Pneumocystis detection immediately after birth suggests the possibility of its transplacental transmission. Comparing to non-colonized infants, more frequent occurrence of bronchopulmonary dysplasia was seen in colonized ones (P=0.02), suggesting a potential clinical importance of this pathogen in abnormal lung development.During space missions, astronauts experience acute and chronic low-dose-rate radiation exposures. Given the clear gap of knowledge regarding such exposures, we assessed the effects acute and chronic exposure to a mixed field of neutrons and photons and single or fractionated simulated galactic cosmic ray exposure (GCRsim) on behavioral and cognitive performance in mice. BMS309403 manufacturer In addition, we assessed the effects of an aspirin-containing diet in the presence and absence of chronic exposure to a mixed field of neutrons and photons. In C3H male mice, there were effects of acute radiation exposure on activity levels in the open field containing objects. In addition, there were radiation-aspirin interactions for effects of chronic radiation exposure on activity levels and measures of anxiety in the open field, and on activity levels in the open field containing objects. There were also detrimental effects of aspirin and chronic radiation exposure on the ability of mice to distinguish the familiar and novel object. Finally, there were effects of acute GCRsim on activity levels in the open field containing objects. Activity levels were lower in GCRsim than sham-irradiated mice. Thus, acute and chronic irradiation to a mixture of neutrons and photons and acute and fractionated GCRsim have differential effects on behavioral and cognitive performance of C3H mice. Within the limitations of our study design, aspirin does not appear to be a suitable countermeasure for effects of chronic exposure to space radiation on cognitive performance.
With increasing use of tranexamic acid in total hip and knee arthroplasties, safety concerns remain. Using national claims data, this study examined tranexamic acid use in patients with preexisting comorbidities. The hypothesis was that tranexamic acid use is not associated with increased complication risk in hip and knee arthroplasty patients with comorbidities.
Among 765,011 total hip/knee arthroplasties (2013 to 2016, Premier Healthcare claims), tranexamic acid use was assessed in three high-risk groups group I with patients with a history of venous thromboembolism, myocardial infarction, seizures, or ischemic stroke/transient ischemic attack (n = 27,890); group II with renal disease (n = 44,608); and group III with atrial fibrillation (n = 45,952). The coprimary outcomes were blood transfusion and new-onset "composite complications" (venous thromboembolism, myocardial infarction, seizures, and ischemic stroke/transient ischemic attack). Associations between tranexamic acid use and outcomes were measured separately by high-risk group.
Website: https://www.selleckchem.com/products/bms309403.html
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