Circadian rhythms originate from molecular feedback loops. In mammals, the transcription factors CLOCK and BMAL1 act on regulatory elements (i.e. E-boxes) to shape biological functions in a rhythmic ...manner. The EPHA4 receptor and its ligands Ephrins (EFN) are cell adhesion molecules regulating neurotransmission and neuronal morphology. Previous studies showed the presence of E-boxes in the genes of
and specific Ephrins, and that
knockout mice have an altered circadian rhythm of locomotor activity. We thus hypothesized that the core clock machinery regulates the gene expression of
,
and
. CLOCK and BMAL1 (or NPAS2 and BMAL2) were found to have transcriptional activity on distal and proximal regions of
,
and
putative promoters. A constitutively active form of glycogen synthase kinase 3β (GSK3β; a negative regulator of CLOCK and BMAL1) blocked the transcriptional induction. Mutating the E-boxes of
distal promoter sequence reduced transcriptional induction. EPHA4 and EFNB2 protein levels did not show circadian variations in the mouse suprachiasmatic nucleus or prefrontal cortex. The findings uncover that core circadian transcription factors can regulate the gene expression of elements of the Eph/Ephrin system, which might contribute to circadian rhythmicity in biological processes in the brain or peripheral tissues.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
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Animal models and archived human biobank tissues are useful resources for research in disease development, diagnostics and therapeutics. For the preservation of microscopic anatomical ...features and to facilitate long‐term storage, a majority of tissue samples are denatured by the chemical treatments required for fixation, paraffin embedding and subsequent deparaffinization. These aggressive chemical processes are thought to modify the biochemical composition of the sample and potentially compromise reliable spectroscopic examination useful for the diagnosis or biomarking. As a result, spectroscopy is often conducted on fresh/frozen samples. In this study, we provide an extensive characterization of the biochemical signals remaining in processed samples (formalin fixation and paraffin embedding, FFPE) and especially those originating from the anatomical layers of a healthy rat colon. The application of chemometric analytical methods (unsupervised and supervised) was shown to eliminate the need for tissue staining and easily revealed microscopic features consistent with goblet cells and the dense populations of cells within the mucosa, principally via strong nucleic acid signals. We were also able to identify the collagenous submucosa‐ and serosa‐ as well as the muscle‐associated signals from the muscular regions and blood vessels. Applying linear regression analysis to the data, we were able to corroborate this initial assignment of cell and tissue types by confirming the biological origin of each layer by reference to a subset of authentic biomolecular standards. Our results demonstrate the potential of using label‐free Raman microspectroscopy to obtain superior imaging contrast in FFPE sections when compared directly to conventional haematoxylin and eosin (H&E) staining.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The behavior of uranium in environments, ranging from those of natural systems responsible for the formation of uranium deposits to those of nuclear reactors providing 11% of the world's electricity, ...is governed by processes involving high-temperature aqueous solutions. It has been well documented that uranium is mobile in aqueous solutions in its oxidized, U
state, whereas in its reduced, U
state, uranium has been assumed to be immobile. Here, we present experimental evidence from high temperature (>100 °C) acidic brines that invalidates this assumption. Our experiments have identified a new uranium chloride species (UCl
°) that is more stable under reducing than oxidized conditions. These results indicate that uranium is mobile under reducing conditions and necessitate a re-evaluation of the mobility of uranium, particularly in ore deposit models involving this metal. Regardless of the scenario considered, reducing conditions can no longer be considered a guarantee of uranium immobility.
Recent interest in U3Si2 as an advanced light water reactor fuel has driven assessment of numerous properties, but characterization of its response to H2O environments is absent from the literature. ...The behavior of U3Si2 in H2O containing atmospheres is investigated and presented in a two-part series of articles aimed to understand the degradation mechanism of U3Si2 in H2O. Reported here are thermogravimetric data for U3Si2 exposed to flowing steam at 250–470 °C. Additionally the response of U3Si2 to flowing Ar-6% H2 from 350 to 400 °C is presented. Microstructural degradation is observed following hours of exposure at 350 °C in steam. U3Si2 undergoes pulverization on the timescale of minutes when temperatures are increased above 400 °C. This mechanism is accelerated in flowing Ar-H2 at the same temperatures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Recent interest in U3Si2 as an advanced light water reactor fuel has driven assessment of numerous properties, but characterization of its response to H2O environments is sparse in available ...literature. The behavior of U3Si2 in H2O containing atmospheres is investigated and presented in a two-part series of articles. This work examines the behavior of U3Si2 following exposure to pressurized H2O at temperatures from 300 to 350 °C. Testing was performed using two autoclave configurations and multiple redox conditions. Use of solid state buffers to attain a controlled water chemistry is also presented as a means to test actinide-bearing systems. Buffers were used to vary the hydrogen concentration between 1 and 30 parts per million H2. Testing included UN, U3Si5, and UO2. Both UN and U3Si5 were found to rapidly pulverize in less than 50 h at 300 °C. Uranium dioxide was included as a control for the autoclave system, and was found to be minimally impacted by exposure to pressurized water at the conditions tested for extended time periods. Testing of U3Si2 at 300 °C found reasonable stability through 30 days in 1–5 ppm H2. However, pulverization was observed following 35 days. The redox condition of testing strongly affected pulverization. Characterization of the resulting microstructures suggests that the mechanism responsible for pulverization under more strongly reducing conditions differs from that previously identified. Hydride formation is hypothesized to drive this transition. Testing performed at 350 °C resulted in rapid pulverization of U3Si2 in under 50 h.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
e24039
Background: Clinical trials are essential in the evaluation of new antineoplastic therapies. However, studies have consistently reported suboptimal levels of clinical trial knowledge among ...adult cancer patients, and less than 5% of them participate in clinical trials. Health information technology (HIT) has shown promise in health promotion and may prove useful in bridging the knowledge gap in clinical trials among cancer survivors. Methods: We obtained data from 3,865 adults who completed the 2020 Health Information National Trends Survey of which 626 (16.2%) were cancer survivors. Using chi-squared tests, we examined the prevalence of HIT use in the general population and by cancer history. We also examined the impact of HIT use on clinical trial knowledge separately for cancer survivors and those with no cancer history using multivariable logistic regression models. Results: 63.8% of cancer survivors reported having some knowledge of clinical trials. Almost half of them used HIT to communicate with doctors (47.1%) and make health appointments (49.4%), about two-fifths (42.2%) used HIT in checking test results and 68.0% reported using HIT to look up health information online. In the adjusted models, the use of HIT in communicating with doctors OR 2.79; 95% CI (1.41, 5.54), checking test results OR 2.47; 95% CI (1.12, 5.43) and looking up health information online OR 2.84; 95% CI (1.04, 7.77) was associated with increased knowledge of clinical trials. Conclusions: Our findings suggest a positive association between HIT utilization and higher clinical trial knowledge levels. These results are encouraging given the rapid increase in mobile technology access globally and the increased use of HIT since the onset of the COVID-19 pandemic. There is a potential opportunity to leverage digital technology in improving clinical trial participation by increasing knowledge levels.
A novel approach was used to understand the effects of processing conditions on the conversion of zirconium dioxide to zirconium carbonitride using a carbothermic reduction to nitridation process. ...The conversion process was studied through the use of thermogravimetric analysis, X-ray diffraction (XRD), and scanning electron microscopy, resulting in an understanding of the nature and progression of conversion. The rate of mass change as measured through thermogravimetric analysis was plotted as a function of reaction progression, guiding the use of XRD in further understanding the conversion process. This approach was then used to characterize the important effect of initial compact morphology on conversion. Coupled analysis techniques allow for advancement of a number of hypotheses regarding the rate-limiting factors along the various steps in the carbothermic reduction to nitridation process. These results demonstrate the value of the proposed approach to aid in deconstruction of competing reaction mechanisms as necessary to understand the system studied here or other systems of scientific and industrial relevance.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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HUH endonucleases (dubbed “HUH‐tags”) are small protein domains capable of forming covalent adducts with ssDNA in a sequence‐specific manner. The active site of HUH endonucleases ...utilizes a conserved histidine‐hydrophobic‐histidine motif to coordinate a metal ion that stabilizes a nucleophilic tyrosine necessary for phosphodiesterase activity. Because viral‐derived HUH‐tags are relatively small, react quickly, and require no chemical modifications to their ssDNA substrate, they have great value as protein fusion tags in biotechnologies ranging from genetic engineering to single‐molecule studies. One of the greatest assets of these tags is sequence‐specificity to their unique, native Ori sequence in vivo, introducing the possibility of using multiple HUH‐tags in multiplexed “one‐pot” reactions. However, their mechanism of ssDNA sequence binding and specificity is poorly understood, and there is noted cross‐reactivity between tags of closely‐related species. In order to understand the mechanism of ssDNA binding, we performed an alanine scan along a positively‐charged patch of one such HUH‐tag, wheat dwarf virus replication initiator protein (WDV), and characterized the enzymatic activity in both the rate and extent of the reaction. In molecular beacon Stopped‐Flow experiments, single point mutants of WDV showed a more than 60% decrease in reaction rate constant, and gel shift assays showed an almost complete lack of activity for some variants for single nucleotide ssDNA substitutions. In all, these findings help us to highlight key interactions in WDV‐ssDNA binding, and we gain further insight into potential rational engineering of HUH‐endonucleases to bind desired sequences of DNA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Lyme disease is a multisystem illness caused by Borrelia burgdorferi, a spirochete transmitted by certain species of Ixodes ticks. Approximately 30,000 confirmed and probable cases of Lyme disease ...were reported in the United States in 2012, primarily from high-incidence states in the Northeast (Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont) and upper Midwest (Minnesota and Wisconsin). Common manifestations include cutaneous, neurologic, and rheumatologic signs and symptoms. Symptomatic infection of the heart is rare in recognized Lyme disease cases and usually resolves promptly with appropriate antibiotic therapy. Nonetheless, cardiac involvement occasionally can cause life-threatening cardiac conduction abnormalities. During November 2012-July 2013, one woman and two men (ranging in age from 26 to 38 years) from high-incidence Lyme disease states experienced sudden cardiac death and, on postmortem examination, were found to have evidence of Lyme carditis. The three deaths were investigated by the Connecticut Department of Public Health, Massachusetts Department of Public Health, New Hampshire Department of Public Health, New York State Department of Health, and CDC. Donated corneas from two decedents had been transplanted to three recipients before the diagnosis of Lyme disease was established, but no evidence of disease transmission was found. Although death from Lyme carditis is rare, it should be considered in cases of sudden cardiac death in patients from high-incidence Lyme disease regions. Reducing exposure to ticks is the best method for preventing Lyme disease and other tickborne infections.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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