Transcription-associated breaks in Xeroderma Pigmentosum group D cells from patients with combined features of Xeroderma Pigmentosum and Cockayne Syndrome

Defects in the XPD gene can result in several clinical phenotypes, including xeroderma pigmentosum (XP), trichothiodystrophy, and, less frequently, the combined phenotype of XP and Cockayne syndrome (XP-D/CS). We previously showed that in cells from two XP-D/CS patients, breaks were introduced into cellular DNA on exposure to UV damage, but these breaks were not at the sites of the damage. In the present work, we show that three further XP-D/CS patients show the same peculiar breakage phenomenon. We show that these breaks can be visualized inside the cells by immunofluorescence using antibodies to either gamma-H2AX or poly-ADP-ribose and that they can be generated by the introduction of plasmids harboring methylation or oxidative damage as well as by UV photoproducts. Inhibition of RNA polymerase II transcription by four different inhibitors dramatically reduced the number of UV-induced breaks. Furthermore, the breaks were dependent on the nucleotide excision repair (NER) machinery. These data are consistent with our hypothesis that the NER machinery introduces the breaks at sites of transcription initiation. During transcription in UV-irradiated XP-D/CS cells, phosphorylation of the carboxy-terminal domain of RNA polymerase II occurred normally, but the elongating form of the polymerase remained blocked at lesions and was eventually degraded

The Effects of Cold and Lower Body Negative Pressure on Cardiovascular Effects

Purpose. The purpose of this study is to determine how cold exposure and lower body negative pressure effected cardiovascular variables. Methods. Eleven males (20.3 years ± 2.7) underwent two 20-minute exposures to LBNP. During the 2 trials, the subjects were exposed to cold air (10°C) (COLD) and to ambient temperature (23°C) (AMB). The trials consisted of a 100-minute pre-LBNP period followed by a 20-minute exposure to LBNP and then a 15-minute recovery period. Cardiovascular variables were recorded every 30 minutes using bioimpedance. Results. When LBNP was applied during the AMB trials, stroke volume immediately decreased. During the COLD trial, there was a five-minute delay before the decrease in stroke volume. Heart rate increased immediately after LBNP initiation during the AMB trials but there was a delay in the increase during the COLD trials. That same pattern was followed with mean arterial blood pressures. Cerebral oxygenation was significantly lower throughout the COLD trial as compared to the AMB trials. Six subjects reported symptoms of syncope or presyncope during the AMB trials but there were no reports of symptoms during the COLD trials. Conclusion. From analysis of this data, cold improved the subject’s tolerance to LBNP

Assessing karyotype precision by microarray-based comparative genomic hybridization in the myelodysplastic/myeloproliferative syndromes

<p>Abstract</p> <p>Background</p> <p>Recent genome-wide microarray-based research investigations have revealed a high frequency of submicroscopic copy number alterations (CNAs) in the myelodysplastic syndromes (MDS), suggesting microarray-based comparative genomic hybridization (aCGH) has the potential to detect new clinically relevant genomic markers in a diagnostic laboratory.</p> <p>Results</p> <p>We performed an exploratory study on 30 cases of MDS, myeloproliferative neoplasia (MPN) or evolving acute myeloid leukemia (AML) (% bone marrow blasts ≤ 30%, range 0-30%, median, 8%) by aCGH, using a genome-wide bacterial artificial chromosome (BAC) microarray. The sample data were compared to corresponding cytogenetics, fluorescence <it>in situ </it>hybridization (FISH), and clinical-pathological findings. Previously unidentified imbalances, in particular those considered submicroscopic aberrations (< 10 Mb), were confirmed by FISH analysis. CNAs identified by aCGH were concordant with the cytogenetic/FISH results in 25/30 (83%) of the samples tested. aCGH revealed new CNAs in 14/30 (47%) patients, including 28 submicroscopic or hidden aberrations verified by FISH studies. Cryptic 344-kb <it>RUNX1 </it>deletions were found in three patients at time of AML transformation. Other hidden CNAs involved 3q26.2/EVI1, 5q22/APC, 5q32/TCERG1,12p13.1/EMP1, 12q21.3/KITLG, and 17q11.2/NF1. Gains of CCND2/12p13.32 were detected in two patients. aCGH failed to detect a balanced translocation (n = 1) and low-level clonality (n = 4) in five karyotypically aberrant samples, revealing clinically important assay limitations.</p> <p>Conclusions</p> <p>The detection of previously known and unknown genomic alterations suggests that aCGH has considerable promise for identification of both recurring microscopic and submicroscopic genomic imbalances that contribute to myeloid disease pathogenesis and progression. These findings suggest that development of higher-resolution microarray platforms could improve karyotyping in clinical practice.</p

Teaching design research through practice: a pilot study for collaborative exploration

As design educators, we experience tension between devoting the precious little time we have in class to educating our students in ways of making (i.e., skills in sewing and patternmaking) and ways of thinking (i.e. design ideation, creativity, etc.)

Evaluation of chronic lymphocytic leukemia by oligonucleotide-based microarray analysis uncovers novel aberrations not detected by FISH or cytogenetic analysis

<p>Abstract</p> <p>Background</p> <p>Cytogenetic evaluation is a key component of the diagnosis and prognosis of chronic lymphocytic leukemia (CLL). We performed oligonucleotide-based comparative genomic hybridization microarray analysis on 34 samples with CLL and known abnormal karyotypes previously determined by cytogenetics and/or fluorescence <it>in situ </it>hybridization (FISH).</p> <p>Results</p> <p>Using a custom designed microarray that targets >1800 genes involved in hematologic disease and other malignancies, we identified additional cryptic aberrations and novel findings in 59% of cases. These included gains and losses of genes associated with cell cycle regulation, apoptosis and susceptibility loci on 3p21.31, 5q35.2q35.3, 10q23.31q23.33, 11q22.3, and 22q11.23.</p> <p>Conclusions</p> <p>Our results show that microarray analysis will detect known aberrations, including microscopic and cryptic alterations. In addition, novel genomic changes will be uncovered that may become important prognostic predictors or treatment targets for CLL in the future.</p

The Vehicle, Spring 1980

Vol. 3, No. 2 Table of Contents White LanguageStarla Stensaaspage 4 The Grand Canyon at SunsetElisabeth Cristpage 5 WitheringSheila Kattypage 5 In Defense of the DandelionKathleen Alakspage 6 HaikuScott Fishelpage 7 Double SolitaireCathy Georgepage 8 AdolescenceNancy Douglaspage 9 Sunrises as SunsetsRobert Schumacherpage 9 War Is Not All HellChris Goerlichpage 11 Young SoldierRobert Swansonpage 11 Without Really Looking For ThemSheila Kattypage 12 JourneyJean Wallacepage 15 I Barely Remember the Poet/TeacherStarla Stensaaspage 16 To SearchKaren Buchananpage 17 Four-Hundred and Twenty-Four DaysAnnette Heinzpage 19 Killing CarpJerry McAnultypage 20 War of the WillsLaurel Anzelmopage 21 Life of a Sexual MetaphorChris Goerlichpage 23 Hazy Days in Mid-JulyKaren Buchananpage 24 August\u27s EndCynthia Rozminpage 24 Visiting GrandmotherRobert Swansonpage 26 UntitledNancy Van Cleavepage 27 The AlbinoDenise Davinroypage 27 This ChristmasRobert Schumacherpage 28 Burnt OfferingGinny Stroheckerpage 29 Long-term VacationDenise Davinroypage 29 Storm\u27s EveJeffrey Stousepage 30 Lovers: A Weaver in the StatesStarla Stensaaspage 31 Gitchegumme BeachScott Fishelpage 32 Dear Husband, What Do You Think?Katherine Adamspage 33 Cat\u27s Eve InnCynthia Rozminpage 34 BassScott Fishelpage 34 Fall Morning in the Okanagan ValleyJerry McAnultypage 35 MusicMary McDanielpage 36 AnticipationNancy Douglaspage 41 Don\u27t Let Your Bread LoafJohn Stockmanpage 41 The FieldElise Hempelpage 42 the g.a.Carla Vitezpage 42 Quality in Search of An AuthorRobert Schinaglpage 43 February 9thLisa Livingstonpage 44 By A Pond in SpringJohn Stockmanpage 46 Night SoundsJeffrey Stousepage 47 Art CoverKaren Dankovich PhotographCindy Hubbarttpage 3 PhotographScott Fishelpage 10 PhotographLisa Larsonpage 18 EtchingKaren Dankovichpage 25 PhotographScott Fishelpage 30 PhotographScott Fishelpage 40 PhotographCindy Hubbarttpage 45 PhotographCindy Hubbarttpage 48https://thekeep.eiu.edu/vehicle/1037/thumbnail.jp

The Vehicle, Spring 1980

Vol. 3, No. 2 Table of Contents White LanguageStarla Stensaaspage 4 The Grand Canyon at SunsetElisabeth Cristpage 5 WitheringSheila Kattypage 5 In Defense of the DandelionKathleen Alakspage 6 HaikuScott Fishelpage 7 Double SolitaireCathy Georgepage 8 AdolescenceNancy Douglaspage 9 Sunrises as SunsetsRobert Schumacherpage 9 War Is Not All HellChris Goerlichpage 11 Young SoldierRobert Swansonpage 11 Without Really Looking For ThemSheila Kattypage 12 JourneyJean Wallacepage 15 I Barely Remember the Poet/TeacherStarla Stensaaspage 16 To SearchKaren Buchananpage 17 Four-Hundred and Twenty-Four DaysAnnette Heinzpage 19 Killing CarpJerry McAnultypage 20 War of the WillsLaurel Anzelmopage 21 Life of a Sexual MetaphorChris Goerlichpage 23 Hazy Days in Mid-JulyKaren Buchananpage 24 August\u27s EndCynthia Rozminpage 24 Visiting GrandmotherRobert Swansonpage 26 UntitledNancy Van Cleavepage 27 The AlbinoDenise Davinroypage 27 This ChristmasRobert Schumacherpage 28 Burnt OfferingGinny Stroheckerpage 29 Long-term VacationDenise Davinroypage 29 Storm\u27s EveJeffrey Stousepage 30 Lovers: A Weaver in the StatesStarla Stensaaspage 31 Gitchegumme BeachScott Fishelpage 32 Dear Husband, What Do You Think?Katherine Adamspage 33 Cat\u27s Eve InnCynthia Rozminpage 34 BassScott Fishelpage 34 Fall Morning in the Okanagan ValleyJerry McAnultypage 35 MusicMary McDanielpage 36 AnticipationNancy Douglaspage 41 Don\u27t Let Your Bread LoafJohn Stockmanpage 41 The FieldElise Hempelpage 42 the g.a.Carla Vitezpage 42 Quality in Search of An AuthorRobert Schinaglpage 43 February 9thLisa Livingstonpage 44 By A Pond in SpringJohn Stockmanpage 46 Night SoundsJeffrey Stousepage 47 Art CoverKaren Dankovich PhotographCindy Hubbarttpage 3 PhotographScott Fishelpage 10 PhotographLisa Larsonpage 18 EtchingKaren Dankovichpage 25 PhotographScott Fishelpage 30 PhotographScott Fishelpage 40 PhotographCindy Hubbarttpage 45 PhotographCindy Hubbarttpage 48https://thekeep.eiu.edu/vehicle/1037/thumbnail.jp

Sera Antibody Repertoire Analyses Reveal Mechanisms of Broad and Pandemic Strain Neutralizing Responses after Human Norovirus Vaccination

Rapidly evolving RNA viruses, such as the GII.4 strain of human norovirus (HuNoV), and their vaccines elicit complex serological responses associated with previous exposure. Specific correlates of protection, moreover, remain poorly understood. Here, we report the GII.4-serological antibody repertoire—pre- and post-vaccination—and select several anti-body clonotypes for epitope and structural analysis. The humoral response was dominated by GII.4-specific antibodies that blocked ancestral strains or by antibodies that bound to divergent genotypes and did not block viral-entry-ligand interactions. However, one antibody, A1431, showed broad blockade toward tested GII.4 strains and neutralized the pandemic GII.P16-GII.4 Sydney strain. Structural mapping revealed conserved epitopes, which were occluded on the virion or partially exposed, allowing for broad blockade with neutralizing activity. Overall, our results provide high-resolution molecular information on humoral immune responses after HuNoV vaccination and demonstrate that infection-derived and vaccine-elicited antibodies can exhibit broad blockade and neutralization against this prevalent human pathogen

Carbon-sensitive pedotransfer functions for plant available water

Currently accepted pedotransfer functions show negligible effect of management-induced changes to soil organic carbon (SOC) on plant available water holding capacity (θAWHC), while some studies show the ability to substantially increase θAWHC through management. The Soil Health Institute\u27s North America Project to Evaluate Soil Health Measurements measured water content at field capacity using intact soil cores across 124 long-term research sites that contained increases in SOC as a result of management treatments such as reduced tillage and cover cropping. Pedotransfer functions were created for volumetric water content at field capacity (θFC) and permanent wilting point (θPWP). New pedotransfer functions had predictions of θAWHC that were similarly accurate compared with Saxton and Rawls when tested on samples from the National Soil Characterization database. Further, the new pedotransfer functions showed substantial effects of soil calcareousness and SOC on θAWHC. For an increase in SOC of 10 g kg–1 (1%) in noncalcareous soils, an average increase in θAWHC of 3.0 mm 100 mm–1 soil (0.03 m3 m–3) on average across all soil texture classes was found. This SOC related increase in θAWHC is about double previous estimates. Calcareous soils had an increase in θAWHC of 1.2 mm 100 mm–1 soil associated with a 10 g kg–1 increase in SOC, across all soil texture classes. New equations can aid in quantifying benefits of soil management practices that increase SOC and can be used to model the effect of changes in management on drought resilience

Linking soil microbial community structure to potential carbon mineralization: A continental scale assessment of reduced tillage

Potential carbon mineralization (Cmin) is a commonly used indicator of soil health, with greater Cmin values interpreted as healthier soil. While Cmin values are typically greater in agricultural soils managed with minimal physical disturbance, the mechanisms driving the increases remain poorly understood. This study assessed bacterial and archaeal community structure and potential microbial drivers of Cmin in soils maintained under various degrees of physical disturbance. Potential carbon mineralization, 16S rRNA sequences, and soil characterization data were collected as part of the North American Project to Evaluate Soil Health Measurements (NAPESHM). Results showed that type of cropping system, intensity of physical disturbance, and soil pH influenced microbial sensitivity to physical disturbance. Furthermore, 28% of amplicon sequence variants (ASVs), which were important in modeling Cmin, were enriched under soils managed with minimal physical disturbance. Sequences identified as enriched under minimal disturbance and important for modeling Cmin, were linked to organisms which could produce extracellular polymeric substances and contained metabolic strategies suited for tolerating environmental stressors. Understanding how physical disturbance shapes microbial communities across climates and inherent soil properties and drives changes in Cmin provides the context necessary to evaluate management impacts on standardized measures of soil microbial activity