Mammalian Hedgehog (HH) signalling pathway plays an essential role in tissue homeostasis and its deregulation is linked to rheumatological disorders. UBR5 is the mammalian homologue of the E3 ...ubiquitin-protein ligase Hyd, a negative regulator of the Hh-pathway in Drosophila. To investigate a possible role of UBR5 in regulation of the musculoskeletal system through modulation of mammalian HH signaling, we created a mouse model for specific loss of Ubr5 function in limb bud mesenchyme. Our findings revealed a role for UBR5 in maintaining cartilage homeostasis and suppressing metaplasia. Ubr5 loss of function resulted in progressive and dramatic articular cartilage degradation, enlarged, abnormally shaped sesamoid bones and extensive heterotopic tissue metaplasia linked to calcification of tendons and ossification of synovium. Genetic suppression of smoothened (Smo), a key mediator of HH signalling, dramatically enhanced the Ubr5 mutant phenotype. Analysis of HH signalling in both mouse and cell model systems revealed that loss of Ubr5 stimulated canonical HH-signalling while also increasing PKA activity. In addition, human osteoarthritic samples revealed similar correlations between UBR5 expression, canonical HH signalling and PKA activity markers. Our studies identified a crucial function for the Ubr5 gene in the maintenance of skeletal tissue homeostasis and an unexpected mode of regulation of the HH signalling pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neospora caninum oocysts, passed in the feces of a definitive host (dog), were isolated, and genomic DNA was extracted. A polymerase cahin reaction (PCR) targeting the N. caninum-specific Nc 5 ...genomic sequence was performed using the isolated DNA. A synthesized competitor molecule containing part of the Nc 5 sequence was included in the assay as a check against false-negative PCR results and to quantify N. caninum oocyst DNA in fecal samples. A standard curve of the ratio of fluorescence intensity of PCR-amplified competitor to that of oocyst DNA was constructed to compare oocyst equivalents from fecal samples containing unknown numbers of N. caninum oocysts and to assess the sensitivity of the assay. The specificity of the assay was determined using the Nc 5–specific primers in PCR assays against other parasites likely to be found in canine feces. Genomic DNA sequences from the canine coccidians Hammondia heydorni, Cryptosporidium parvum, Sarcocystis cruzi, S. tenella, and Isospora ohioensis and the canine helminth parasites Strongyloides stercoralis, Toxocara canis, Dipylidium caninum, and Ancylostoma caninum were not amplified. In addition, genomic DNA sequences from oocysts of coccidian parasites that might contaminate dog feces, such as Hammondia hammondi, Toxoplasma gondii, or Eimeria tenella, were not amplified in the PCR assay. The assay should be useful in epidemiological surveys of both domestic and wild canine hosts and in investigations of oocyst biology in experimental infections.
A practical method is proposed for the fast shutdown of a large ignited tokamak. The method consists of injecting a rapid series of 30-45 (6 mm) deuterium pellets doped with a small (0.0005%) ...concentration of krypton impurity, and simultaneously ramping the plasma current and shaping fields down over a period of several seconds using the poloidal field system. Detailed modelling with the Tokamak Simulation Code using a newly developed pellet mass deposition model shows that this method should terminate the discharge in a controlled and stable way without producing significant numbers of runaway electrons. A partial prototyping of this technique was accomplished in TFTR.
Statius Hill, D. E.
The Classical Review,
10/2005, Letnik:
55, Številka:
2
Journal Article, Book Review
Recenzirano
Mozley's 1928 Loeb edition of the Statian corpus took up 1203 pages in two volumes. The following edition takes up 1352 pages in three volumes, with the first devoted only to the "Silvae": "Statius: ...Thebaid, Books 1-7. Introduction, Text and Translation", edited and translated by D.R. Shackleton Bailey; "Statius: Thebaid, Books 8-12, Achilleid. Text, Translation, and Indexes", edited and translated by D.R. Shackleton Bailey; and "Publius Papinius Statius: The Thebaid. Seven against Thebes. Translated with an introduction" by C.S. Ross. Buyers may be mollified by the inclusion of a superb essay on recent scholarship by Kathleen Coleman with full biography. Mozley's edition had no index; Shackleton Bailey's has two indexes of proper names, one for the "Thebaid", the other for the "Achilleid".
The annual National Conference on Health Disparities (NCHD) was launched in 2000. It unites health professionals, researchers, community leaders, and government officials, and is a catalyzing force ...in developing policies, research interventions, and programs that address prevention, social determinants, health disparities, and health equity. The NCHD Student Research Forum (SRF) was established in 2011 at the Medical University of South Carolina to build high-quality biomedical research presentation capacity in primarily underrepresented undergraduate and graduate/professional students. This paper describes the unique research training and professional development aspects of the NCHD SRF. These include guidance in abstract development, a webinar on presentation techniques and methods, a vibrant student-centric conference, and professional development workshops on finding a mentor and locating scholarship/fellowship funding, networking, and strategies for handling ethical issues in research with mentors. Between 2011 and 2018, 400 undergraduate and graduate/professional students participated in the NCHD SRF. Most students were women (80.5%). Approximately half were African American or black (52.3%), 18.0% were white, and 21.3% were of Hispanic/Latinx ethnicity. The NCHD SRF is unique in several ways. First, it provides detailed instructions on developing a scientific abstract, including content area examples. Second, it establishes a mandatory pre-conference training webinar demonstrating how to prepare a scientific poster. Third, it works with the research mentors, faculty advisors, department chairs, and deans to help identify potential sources of travel funding for students with accepted abstracts. These features make the NCHD SRF different from many other conferences focused on students’ scientific presentations.
Vasoactive intestinal peptide, a trophic and mitogenic factor, stimulates growth in whole cultured mouse embryos. Inhibition of this growth function between embryonic days 9 and 11 induces growth ...retardation accompanied by severe microcephaly. In the present study, to determine the effects of this peptide on the different phases of the cell cycle of neural cells, embryonic day 9.5 cultured mouse embryos were cumulatively labelled with bromodeoxyuridine. Vasoactive intestinal peptide (10–7m) shortened S phase and G1 phase of neuroepithelial cells by 50% (4.8–2.4 h) and 58% (1.9–0.8 h), respectively, compared with controls. G2 and M phases were not modified by vasoactive intestinal peptide treatment. Total cell cycle length was consequently reduced by 43% (8.2–4.7 h) in vasoactive intestinal peptide treated embryos, compared with controls. In contrast, vasoactive intestinal peptide did not modify the rate of neuroepithelial cell death as assessed by the proportion of nuclei containing fragmented DNA. These data suggest that vasoactive intestinal peptide stimulates growth in premigratory stages of nervous system development by shortening S and G1 phases of the cell cycle and that S phase duration can be regulated by a physiological peptide.
Activation of a facultative, dicentric chromosome provides a unique opportunity to introduce a double strand DNA break into a chromosome at mitosis. Time lapse video enhanced-differential ...interference contrast analysis of the cellular response upon dicentric activation reveals that the majority of cells initiates anaphase B, characterized by pole-pole separation, and pauses in mid-anaphase for 30-120 min with spindles spanning the neck of the bud before completing spindle elongation and cytokinesis. The length of the spindle at the delay point (3-4 micrometers) is not dependent on the physical distance between the two centromeres, indicating that the arrest represents surveillance of a dicentric induced aberration. No mid-anaphase delay is observed in the absence of the RAD9 checkpoint gene, which prevents cell cycle progression in the presence of damaged DNA. These observations reveal RAD9-dependent events well past the G2/M boundary and have considerable implications in understanding how chromosome integrity and the position and state of the mitotic spindle are monitored before cytokinesis
Abstract Ischemic mitral regurgitation (MR) has been associated with worse outcome myocardial infarction. However, severity of MR and its impact on patients with STEMI undergoing primary PCI remains ...unknown. We sought to determine impact of increasing severity of ischemic MR on outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). All patients presenting with STEMI who underwent primary PCI within 12 hours of symptoms from 1994-2014 were included. Ischemic MR was graded from 0 to 4+ within 3 days of index MI by echocardiography. Overall, 4,005 STEMI patients were included. None, 1+, 2+, 3+ and 4+ MR was present in 3,200 (79.9%), 427 (10.7%), 260 (6.5%), 91 (2.3%) and 27 (0.7%) patients, respectively. On Multivariate logistic regression analysis, more severe MR was associated with older age, female gender, lower body mass index, anemia, inferior STEMI and longer door-to-balloon time (DBT). The 30-day mortality was 6.8, 7.3, 8.8, 19.8 and 26.1%, respectively, with increasing grade of MR. The 1-year mortality rate was 10.8, 12.4, 20.8, 37.4 and 37.1%, while 5-year mortality rates were 16.2, 23.1, 36.5, 53.8 and 63%, respectively (p<0.001 all) for none to 4+ MR. After adjusting for age, gender, co-morbidities, ejection fraction and shock by multivariate analysis, severity of ischemic MR was associated with incremental effect on long-term mortality (HR of 1.42, 1.83, 2.41 and 2.95 for 1+ to 4+ MR respectively, p <0.01 for all). In conclusion, higher grades of MR in patients with STEMI undergoing primary PCI are associated with worse short- and long-term outcomes.
Plant-derived polyphenolics and other chemicals with antioxidant properties have been reported to inhibit the expression of genotoxic activity by pro-oxidant chemicals (
Sai et al. 1992, 1994;
Teel ...and Castonguay, 1992).
In vitro and
in vivo studies with ionizing radiation suggest that hydroquinone (HQ) may have similar protective effects (
Babaev et al., 1994). The present study was conducted to determine whether HQ is capable of inhibiting the induction of micronuclei in the bone marrow of mice following exposure to an oxidant, potassium bromate or KBrO
3 (
Nakajima et al., 1989;
Sai et al. 1992, 1994). To be able to interpret the results of this work, it was also necessary to determine whether HQ is itself genotoxic when fed in the diet. HQ diets (0.8%) fed to mice for 6 days reduced the background incidence of micronuclei compared with the basal diet. KBrO
3 dosed ip (12.5–100
mg/kg) produced a dose-dependent increase in micronuclei as reported by others. Mice fed 0.8% HQ diets 6 days, and then dosed intraperitoneally with KBrO
3, showed a 36% reduction in micronuclei across the range of KBrO
3 dose levels. This effect was associated with a reduction in the background micronucleus response as well as a reduction in response to KBrO
3. Statistical significance (
P⩽0.05), observed at a dose of 25
mg/kg KBrO
3 in the mice fed the control diet, was abolished in the group fed 0.8% HQ. When mice were given 50
mg HQ/kg by oral gavage and then given 50
mg KBrO
3/kg ip 20
min later, the micronucleus response induced by KBrO
3, was lower in animals given HQ. The results of this study demonstrate that large doses of HQ may be given orally without induction of micronuclei or bone marrow depression, that HQ reduces the background micronucleus response in animals fed a basal diet, and that the HQ reduces the micronucleus response to KBrO
3 as well as background incidence of micronuclei in KBrO
3-dosed animals. The protective effect of HQ may be due to enzyme induction or a direct antioxidant effect of HQ against oxidants commonly present in the diet.
The objective was to quantify the effect of breed composition on sale price of steer and heifer calves sold through a single livestock video auction service from 2010 through 2016.
Data were ...available from steer (29,103 lots) and heifer (18,955 lots) calves sold in 164 unique video auctions through one livestock video auction service. A multiple regression model using a backward selection procedure was developed for each calf sex to quantify effects of independent factors on sale price. A value of P < 0.05 was used to maintain a factor in the final model. Lots of calves were categorized into 1 of 6 breed groups: English and English-crossed, English–Continental crossed, Black Angus-sired calves out of dams with no Brahman influence, Red Angus-sired calves out of dams with no Brahman influence, Charolais-sired calves out of dams with no Brahman influence, and Brahman influenced.
Breed description of steer and heifer calf lots affected sale price (P < 0.0001). Among heifers, Red Angus-sired calves had the greatest (P < 0.05) sale price ($173.88/45.36 kg of BW) compared with heifers of other breed groups. Among steers, Charolais-sired calves ($179.09/45.36 kg of BW) were similar (P = 0.19) in value to Red Angus-sired calves ($177.86/45.36 kg of BW) and greater (P < 0.05) than Black Angus-sired calves ($177.23/45.36 kg of BW).
Sire breeds selected, buyer preferences, and marketing venues of both steer and heifer calves should be considered holistically by producers so maximal calf values are realized when sold.
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