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Global warming has been shown to harmfully affect symbiosis between Symbiodiniaceae and other marine invertebrates. When symbiotic dinoflagellates (the genus Breviolum) were in vitro exposed to acute heat stress of +7 °C for a period of 5 days, the results revealed the negative impact on all physiological and other cellular parameters measured. Elevated temperatures resulted in a severe reduction in algal density of up to 9.5-fold, as well as pigment concentrations, indicating the status of the physiological stress and early signs of photo-bleaching. Reactive oxygen species (ROS) were increased in all heated dinoflagellate cells, while the antioxidant-reduced glutathione levels initially dropped on day one but increased under prolonged temperature stress. The cell viability parameters were reduced by 97 % over the heating period, with an increased proportion of apoptotic and necrotic cells. Autofluorescence (AF) for Cy5-PE 660-20 was reduced from 1.7-fold at day 1 to up to 50-fold drop at the end of heating time, indicating that the AF changes were highly sensitive to heat stress and that it could be an extremely sensitive tool for assessing the functionality of algal photosynthetic machinery. The addition of the drug 5-AZA-2'-deoxycytidine (5-AZA), which inhibits DNA methylation processes, was assessed in parallel and contributed to some alterations in algal cellular stress response. The presence of drug 5-AZA combined with the temperature stress had an additional impact on Symbiodiniaceae density and cell complexity, including the AF levels. These variations in cellular stress response under heat stress and compromised DNA methylation conditions may indicate the importance of this epigenetic mechanism for symbiotic dinoflagellate thermal tolerance adaptability over a longer period, which needs further exploration. Consequently, the increased ROS levels and changes in AF signals reported during ongoing heat stress in dinoflagellate cells could be used as early stress biomarkers in these microalgae and potentially other photosynthetic species., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Targeted protein degradation offers new opportunities to inactivate cancer drivers and has successfully entered the clinic. Ways to induce selective protein degradation include proteolysis targeting chimera (PROTAC) technology and immunomodulatory (IMiDs) / next-generation Cereblon (CRBN) E3 ligase modulating drugs (CELMoDs). Here, we aimed to develop a MYC PROTAC based on the MYC-MAX dimerization inhibitor 10058-F4 derivative 28RH and Thalidomide, called MDEG-541. We show that a subgroup of gastrointestinal cancer cell lines and primary patient-derived organoids are MDEG-541 sensitive. Although MYC expression was regulated in a CRBN-, proteasome- and ubiquitin-dependent manner, we provide evidence that MDEG-541 induced the degradation of CRBN neosubstrates, including G1 to S phase transition 1/2 (GSPT1/2) and the Polo-like kinase 1 (PLK1). In sum, we have established a CRBN-dependent degrader of relevant cancer targets with activity in gastrointestinal cancers., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

It's more than just luck: A qualitative exploration of breastfeeding in rural Australia PROBLEM: Despite significant public health benefits, breastfeeding for six months continues to be challenging for women., Background: In the Mid North of South Australia, healthcare professionals were concerned that breastfeeding rates were lower than the national average and that a collaborative approach was needed to promote breastfeeding., Aim: To explore the experiences of women and health professional in the Mid North, to inform interventions to improve breastfeeding longevity., Method: Two focus groups were conducted to examine breastfeeding experience in the region. Focus group one included nine mothers who had breastfed more than six months and focus group two consisted of ten health professionals from the Mid North. Thematic analysis was used to analyse the data., Findings: Two overarching themes were identified; 'breastfeeding: It's more than just luck' represented the voices of the mothers and 'breastfeeding: It's everybody's business' captured the discussion between the health professionals. Women described themselves as lucky while acknowledging that their own persistence, as well as positive support was vital. Health professionals identified education and support as key foci, and a need for a holistic approach to improve breastfeeding rates., Discussion: Breastfeeding should be understood as a relationship, in which broadly applied solutions do not necessarily influence longevity, particularly in rural communities. Strategies should also reflect a realistic picture of breastfeeding and safeguard against idealistic expectation of the experience., Conclusion: A holistic approach to improve breastfeeding rates is imperative. One of the most promising antidotes to the breastfeeding dilemma is the provision of midwifery continuity of care., (Copyright © 2017. Published by Elsevier Ltd.)

Coral reef macroalgae are expected to thrive in the future under conditions that are deleterious to the health of reef-building corals. Here we examined how macroalgae would be affected by exposure to future CO 2 emission scenarios (pCO 2 and temperature), enriched nutrients and combinations of both. The species tested, Laurencia intricata (Rhodophyta), Turbinaria ornata and Chnoospora implexa (both Phaeophyceae), have active carbon-concentrating mechanisms but responded differently to the treatments. L. intricata showed high mortality under nutrient enriched RCP4.5 ("reduced" CO 2 emission) and RCP8.5 ("business-as-usual" CO 2 emission) and grew best under pre-industrial (PI) conditions, where it could take up carbon using external carbonic anhydrase combined, potentially, with proton extrusion. T. ornata's growth rate showed a trend for reduction under RCP8.5 but was unaffected by nutrient enrichment. In C. implexa, highest growth was observed under PI conditions, but highest net photosynthesis occurred under RCP8.5, suggesting that under RCP8.5, carbon is stored and respired at greater rates while it is directed to growth under PI conditions. None of the species showed growth enhancement under future scenarios, nutrient enrichment or combinations of both. This leads to the conclusion that under such conditions these species are unlikely to pose an increasing threat to coral reefs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Interleukin-1 receptor type I (IL-1RI) belongs to a superfamily of proteins characterized by an intracellular Toll/IL-1 receptor (TIR) domain. This domain harbors three conserved regions called boxes 1-3 that play crucial roles in mediating IL-1 responses. Boxes 1 and 2 are considered to be involved in binding of adapter molecules. Amino acids possibly crucial for IL-1RI signaling were predicted via homology models of the IL-1RI TIR domain based on the crystal structure of IL-1RAPL. The role of ten of these residues was investigated by site-directed mutagenesis and a functional luciferase assay reflecting NF-κB activity in transiently transfected Jurkat cells. In particular, the mutants E437K/D438K, E472A/E473A and S465A/S470A/S471A/E472A/E473A showed decreased and the mutant E437A/D438A increased IL-1 responsiveness compared to the mouse IL-1RI wild type. In conclusion, the αC' helix (Q469-E473 in mouse IL-1RI) is probably involved in heterotypic interactions of IL-1RI with IL-1RAcP or MyD88., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this research was to develop a simple quality assurance phantom that could be used for the initial calibration and follow-up testing of commercially available intraoral digital imaging systems., Study Design: A radiographic phantom was constructed that contains a calibrated step wedge for measuring dose response, an etched pattern of slits in a metallic background for measuring the spatial resolution in line pairs per millimeter, and 2 rows of wells of varying diameter and depth in an acrylic background for contrast-detail analysis. Quality assurance protocols were developed and validated., Results: The quality assurance phantom provides a method of assessing a digital intraoral imaging system by measuring the sensitivity and dynamic range, the contrast/detail detectability and the spatial resolution., Conclusions: This quality assurance phantom can serve as an effective means to calibrate and monitor the performance characteristics of a digital dental intraoral imaging system., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Introduction: As digital imaging improves and digital cephalometric radiography becomes more prevalent, the need for digital storage space and transmission speed will increase. Compression of the image files is 1 method to overcome transmission overload. However, compression could compromise image quality. The purpose of this study was to determine the range of compression ratios, by using the JPEG2000 standard, within which the identification of landmarks on cephalometric radiographs is not compromised., Methods: Ten lateral cephalometric digital images were used. Six raters identified 19 landmarks under controlled viewing conditions. The images included the original uncompressed TIFF image and the JPEG2000 format at 3:1, 12:1, 50:1, and 110:1 compression ratios. The images were randomized and displayed with image processing software. The x and y coordinates of each landmark were recorded., Results: All compression ratios performed equally well compared with the original images with the exception of A-point and nasion at 110:1 and gonion at 3:1 compression ratios. All landmark identifications were precise with the exception of the maxillary incisal apex and edge at the 12:1 and 50:1 compression ratios, respectively., Conclusions: JPEG2000 is a reliable file format that can be implemented in orthodontic practice., (Copyright © 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

The green fluorescent protein (avGFP), its variants, and the closely related GFP-like proteins are characterized structurally by a cyclic tri-peptide chromophore located centrally within a conserved beta-can fold. Traditionally, these GFP family members have been isolated from the Cnidaria although recently, distantly related GFP-like proteins from the Bilateria, a sister group of the Cnidaria have been described, although no representative structure from this phylum has been reported to date. We have determined to 2.1A resolution the crystal structure of copGFP, a representative GFP-like protein from a copepod, a member of the Bilateria. The structure of copGFP revealed that, despite sharing only 19% sequence identity with GFP, the tri-peptide chromophore (Gly57-Tyr58-Gly59) of copGFP adopted a cis coplanar conformation within the conserved beta-can fold. However, the immediate environment surrounding the chromophore of copGFP was markedly atypical when compared to other members of the GFP-superfamily, with a large network of bulky residues observed to surround the chromophore. Arg87 and Glu222 (GFP numbering 96 and 222), the only two residues conserved between copGFP, GFP and GFP-like proteins are involved in autocatalytic genesis of the chromophore. Accordingly, the copGFP structure provides an alternative platform for the development of a new suite of fluorescent protein tools. Moreover, the structure suggests that the autocatalytic genesis of the chromophore is remarkably tolerant to a high degree of sequence and structural variation within the beta-can fold of the GFP superfamily.

Brain norepinephrine (NE) modulates many aspects of the stress response. The interaction between NE and neuropeptides such as galanin, with which it is closely associated and which may be released from noradrenergic terminals under conditions of high activity, has not been well studied. We therefore investigated the modulatory effects of galanin in the central nucleus of the amygdala (CeA) on behavioral responsivity to stress when activation of the noradrenergic system was amplified using the adrenergic autoreceptor antagonist yohimbine (2.5 mg/kg ip). Either immobilization stress or yohimbine alone had anxiogenic effects on rat behavior in the elevated plus maze. However, yohimbine pretreatment before stress produced a paradoxical anxiolytic response, which we hypothesized was attributable to galanin release in CeA. Microdialysis verified that yohimbine amplified NE release in CeA during immobilization stress, and also showed that whereas there was no detectable change in galanin release in CeA during stress alone, there was an increase during immobilization stress after yohimbine pretreatment. Bilateral administration of the galanin antagonist M40 into CeA before stress blocked the anxiolytic influence of yohimbine pretreatment. Exogenous galanin mimicked the anxiolytic effect of yohimbine pretreatment, and this too was blocked by M40. These results suggest that amplifying the noradrenergic response to stress can recruit galanin release in CeA, which buffers the anxiety-like behavioral response to acute stress. The balance between noradrenergic and peptidergic neurotransmission may be modified by prior stress, drug treatment or genetic variability, and may represent a novel target for treatment of stress-related neuropsychiatric disorders.

In systemic vasculitis, interactions between antineutrophil cytoplasm autoantibodies (ANCAs) and neutrophils initiate endothelial and vascular injury. ANCAs directed against either myeloperoxidase (MPO) or proteinase 3 (PR3) can activate cytokine-primed neutrophils by binding cell surface-expressed MPO or PR3, with the concurrent engagement of Fcgamma receptors (FcgammaR). Because roles for phospholipase D (PLD) and phosphatidylinositol 3 kinase (PI3K) have been demonstrated in FcgammaR activation of neutrophils, this study investigated the hypothesis that ANCA stimulation of neutrophils involved a similar engagement of FcgammaR and activation of PLD and PI3K. Pretreatment of tumor necrosis factor (TNF) alpha-primed neutrophils with antibodies against FcgammaRII and FcgammaRIII inhibited MPO-ANCA and PR3-ANCA induced superoxide generation, confirming that FcgammaR ligation is involved in ANCA-mediated neutrophil activation. However, although stimulation of TNF-alpha-primed neutrophils by conventional FcgammaR ligation, either using antibody-mediated cross-linking of FcgammaR or aggregated IgG, induced PLD activation, ANCA stimulation did not. Moreover, although ANCA-induced neutrophil activation results in significant PI3K activation-as assessed by phosphatidylinositol 3,4,5-triphosphate generation-conventional FcgammaR ligation, but not ANCA, activates the p85/p110 PI3K subtype. Inhibition of ANCA-induced superoxide generation with pertussis toxin suggests that ANCAs activate the p101/p110gamma PI3K isoform. In addition, the kinetics of activation of protein kinase B differs between conventional FcgammaR ligation and ANCA stimulation of neutrophils. These results demonstrate that though ligation of FcgammaRIIa and FcgammaRIIIb may be necessary, it is likely that ANCAs require other membrane cofactors for neutrophil activation.

Objective: The purpose of this study was to compare a new digital subtraction system with conventional radiograph images for the detection of periapical and periodontal bone lesions., Study Design: Periapical and periodontal bone lesions were simulated with cortical bone chips of varying sizes placed on a human dry mandible. Radiographic film images were acquired from varying projections and were subsequently digitized, registered, and subtracted. Four clinicians evaluated the subtracted images, and sensitivity and specificity were calculated., Results: The mean sensitivity and specificity of the Diagnostic Subtraction Radiography system for detecting bone lesions of all sizes with varying projection geometry were 87.90% and 85.23%, respectively. The corresponding results for conventional radiograph images were 47.54% and 97.38%. The difference in sensitivity was statistically significant, whereas the difference in specificity was not., Conclusions: These results indicate that, even when radiographs are taken from disparate projection geometries, the Diagnostic Subtraction Radiography system is capable of excellent discrimination between healthy and disease states in this in vitro model.

Background: This study evaluated the efficacy of combined intermittent and continuous treatment with diluted sodium hypochlorite, or NaClO, to improve dental unit water quality in a clinical setting., Methods: In this prospective study, 10 dental units were fitted with separate water reservoir systems. Dental units were maintained with weekly rinses with 1:10 NaClO. Treatment water consisted of 750 milliliters of tap water and one drop of undiluted commercial bleach. Bacterial contamination in the effluent coolant water was assayed via microbiologic culture on a weekly basis. At the end of the study, scanning electron microscopy of the inner surfaces of the dental unit waterlines corroborated the results., Results: All 10 dental units consistently delivered water with less than 10 colony-forming units per milliliter, or CFU/mL, with a mean bacterial contamination of less than 1 CFU/mL. Baseline scanning electron microscopy demonstrated biofilm formation. Scanning electron microscopy at the end of the study demonstrated the lack of features consistent with biofilm formation. Although tri-halomethanes were detected in output water, all samples were below Environmental Protection Agency limits for drinking water., Conclusions: Weekly treatment with 5.25 percent NaClO diluted 1:10, and concomitant use of chlorinated treatment water (3 parts per million chlorine) consistently attained the proposed American Dental Association goal of fewer than 200 CFU/mL in the unfiltered output. The effects of continuous treatment on dentin and enamel bond strength may require further evaluation., Clinical Implications: The success of this protocol suggests that optimal attainment of dental water quality goals may require a combination of approaches.

The authors conducted a study to determine the sensitivity, specificity and accuracy of HPC Samplers (Millipore Corp.) as compared with that of R2A agar and HPC agar when used to monitor dental unit water, or DUW, quality. Results were either a pass (200 colony-forming units per milliliter, or CFU/mL, or less) or a fail (greater than 200 CFU/mL). Of the 408 tests conducted, the results of the HPC Sampler agreed with R2A agar 377 times, for an accuracy rate of 92.6 percent. The authors recommend that clinicians consider using HPC Samplers, as they are a user-friendly, economical means of monitoring compliance of DUW quality.

Sealer placement techniques have not been examined in teeth with curved canals prepared with Lightspeed instruments. Three traditional methods of placing sealer were studied, using 45 extracted human single-rooted teeth, divided into 3 groups of 15. Root canal preparations were made with Light-speed nickel-titanium, engine-driven instruments. AH26 sealer was applied with either K-file, lentulo spiral, or master gutta-percha cone. Radiographs were taken after sealer placement and analyzed for amount of canal sealer fill. The teeth were then obturated with laterally condensed gutta-percha, chemically cleared, photographed, and analyzed for total canal wall sealer coverage. The results showed a statistically significant difference in canal sealer fill among the three groups before obturation, but there was no statistical difference in canal wall coverage among the three groups after obturation. None of the examined methods exceeded an average of 62.5% wall coverage of sealer after obturation. This suggests that complete wall coverage after obturation may not be possible.

Thirty-six mesial canals in 18 extracted human mandibular molars were randomly allocated to three experimental groups. Specimens were prepared and evaluated using a modified Bramante technique. Teeth were sectioned at the midroot and apical regions. Canals were prepared with the Lightspeed instruments rotating at 750, 1300, or 2000 rpm. Digitized uninstrumented and instrumented canal images were compared via subtraction software. There was no significant difference (p <0.05) among the three experimental groups in the amount of dentin removed, canal transportation, or the ability of the instrument to remain centered in the canal.

Immediate access to off-site expert diagnostic consultants regarding unusual radiographic findings or radiographic quality assurance issues could be a current problem for private dental practitioners. Teleradiology, a system for transmitting radiographic images, offers a potential solution to this problem. Although much research has been done to evaluate feasibility and utilization of teleradiology systems in medical imaging, little research on dental applications has been performed. In this investigation 47 panoramic films with an equal distribution of images with intraosseous jaw lesions and no disease were viewed by a panel of observers with teleradiology and conventional viewing methods. The teleradiology system consisted of an analog video-based system simulating remote radiographic consultation between a general dentist and a dental imaging specialist. Conventional viewing consisted of traditional viewbox methods. Observers were asked to identify the presence or absence of 24 intraosseous lesions and to determine their locations. No statistically significant differences in modalities or observers were identified between methods at the 0.05 level. The results indicate that viewing intraosseous lesions of video-based panoramic images is equal to conventional light box viewing.

To study the noise characteristics of the Sens-A-Ray (Regam Medical Systems AB, Sundsvall, Sweden) system, 20 radiographs were obtained at each of three different exposure levels at 70 and 90 kVp with a homogeneous x-ray field. Exposures were measured with an ionization chamber. Noise power spectra were calculated over three areas within each radiograph, and ensemble averages were subsequently found from 60 data files at each exposure level. Noise equivalent quanta were calculated with the noise power spectra and modulation transfer function data from previous studies. Finally, the detective quantum efficiency was calculated by dividing the noise equivalent quanta by the estimated incident photon fluence at the different exposures. The system has a maximum detective quantum efficiency of approximately 0.030 at 70 kVp and 0.025 at 90 kVp. A broad maximum exists at approximately 2 cycles/mm, indicating that the signal-to-noise ratio is most favorable at this spatial frequency.

Several types of GTP-binding proteins exist in plant cells. These include the ras-related low-molecular-weight monomeric GTP-binding proteins and the multi-subunit group which more closely resembles members of the mammalian heterotrimeric G-protein family. Proteins belonging to both of these families are known to be involved in cell signalling events and have until recently been assumed to be associated predominantly with membranes. We have investigated the possibility that GTP-binding proteins in plants also can be associated with membrane-free carrot (Daucus carota L.) cytoskeletons and nuclear matrices. Our results demonstrate that several low-molecular-weight GTP-binding proteins, and at least one G-protein alpha-subunit homologue, are associated with these cellular compartments.

This study used a modified Bramante technique and new digital subtraction software to compare root canals prepared by nickel-titanium (Ni-Ti) hand, Ni-Ti engine-driven, and stainless steel hand endodontic instruments. Sixty mesial canals of extracted human mandibular molars were randomly divided into five groups. The roots were embedded in clear resin and cross-sectioned in the apical and mid-root areas. In group A, canals were instrumented using a quarter turn/pull technique with K-Flex files. In group B, canals were prepared with Ni-Ti hand files (Mity files) using the same technique as in group A. Group C was prepared with NT Sensor engine-driven files. Group D canals were prepared with Ni-Ti Canal Master "U" hand instruments. Group E was prepared with engine-driven Ni-Ti Lightspeed instruments. Digitized images of the uninstrumented canals were compared with images of the instrumented canals. Engine-driven Ni-Ti instruments (Lightspeed and NT Sensor file) and hand instrumentation with the Canal Master "U" caused significantly less canal transportation (p < 0.05), remained more centered in the canal (p < 0.05), removed less dentin (p < 0.05), and produced rounder canal preparations than K-Flex and Mity files. Engine instrumentation with Lightspeed and NT Sensor file was significantly faster than hand instrumentation (p < 0.05).

This research compared the length determination images produced by Trophy and Regam direct digital radiographic systems with conventional E-speed radiographs. Size #15 K files were placed in the canals of 19 teeth of cadaver specimens and radiographed in a geometrically standardized bench device. Three evaluators estimated the length adjustment necessary to position the file at the apex. The mean estimated adjustment lengths were compared with the true, anatomically determined adjustment lengths. Statistical analysis with analysis of variance and the Student-Newman-Keuls test indicated no significant difference between direct digital thermal print images and conventional radiographs (p > 0.10). Length adjustment estimates with conventional radiographs were significantly more accurate than Regam high-resolution computer monitor images (p < 0.01). Additionally, it was determined that length adjustment estimates were significantly more accurate when the file was placed short of the apex (p < 0.001). The clinical relevance of these differences is discussed.

Digital subtraction radiography was investigated for its capability to detect and quantify experimentally produced external root resorptive defects in teeth. Using a long source to object X-ray technique and E-speed film, serial radiographs of teeth with artificial lesions in a dry human skull (soft tissue simulated) were obtained. Receiver operating characteristic analysis was used to evaluate the diagnostic performance for each imaging system (conventional versus subtraction). To explore the quantitative assessment potential of digital subtraction radiography, images were produced after sequential demineralization by HCl. The acid solution was analyzed for calcium concentration by atomic absorption spectrophotometry. Three-dimensional histogram quantification for each subtracted image was performed. In overall performance for detecting experimentally produced external root resorption, digital subtraction radiography was found to be significantly superior to conventional radiography. In addition, digital subtraction radiography can provide quantification of experimentally produced external root resorptive defects.