Abstract
Objectives
To assess current pathology resident training in genomic and molecular pathology.
Methods
The Training Residents in Genomics (TRIG) Working Group has developed survey questions ...for the pathology Resident In-Service Examination (RISE) since 2012. Responses to these questions, as well as knowledge questions, were analyzed.
Results
A total of 2,529 residents took the 2019 RISE. Since 2013, there has been an increase in postgraduate year 4 (PGY4) respondents indicating training in genomic medicine (58% to approximately 80%) but still less than almost 100% each year for molecular pathology. In 2019, PGY4 residents indicated less perceived knowledge and ability related to both genomic and traditional molecular pathology topics compared with control areas. Knowledge question results supported this subjective self-appraisal.
Conclusions
The RISE is a powerful tool for assessing the current state and also trends related to resident training in genomic pathology. The results show progress but also the need for improvement in not only genomic pathology but traditional molecular pathology training as well.
To formulate more accurate guidelines for musculoskeletal disorders (MSD) linked to
Hand-Arm Vibration Syndrome (HAVS), delineation of the response of bone tissue under
different frequencies and ...duration of vibration needs elucidation. Rat-tails were vibrated
at 125 Hz (9 rats) and 250 Hz (9 rats), at 49 m/s
2
, for 1D (6 rats), 5D (6
rats) and 20D (6 rats); D=days (4 h/d). Rats in the control group (6 rats for the
vibration groups; 2 each for 1D, 5D, and 20D) were left in their cages, without being
subjected to any vibration. Structural and biochemical damages were quantified using empty
lacunae count and nitrotyrosine signal-intensity, respectively. One-way repeated-measure
mixed-model ANOVA at
p
<0.05 level of significance was used for
analysis. In the cortical bone, structural damage quantified through empty lacunae count
was significant (
p
<0.05) at 250 Hz (10.82 ± 0.66) in comparison to the
control group (7.41 ± 0.76). The biochemical damage was significant
(
p
<0.05) at both the 125 Hz and 250 Hz vibration frequencies. The
structural damage was significant (
p
<0.05) at 5D for cortical bone
while the trabecular bone showed significant (
p
<0.05) damage at 20D
time point. Further, the biochemical damage increased with increase in the duration of
vibration with a significant (
p
<0.05) damage observed at 20D time
point and a near significant change (
p
=0.08) observed at 5D time point.
Structural and biochemical changes in bone tissue are dependent upon higher vibration
frequencies of 125 Hz, 250 Hz and the duration of vibration (5D, 20D).
Involvement of mast cells in eosinophilic esophagitis Abonia, J. Pablo, MD; Blanchard, Carine, PhD; Butz, Bridget Buckmeier, MHSA ...
Journal of allergy and clinical immunology,
07/2010, Letnik:
126, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background Eosinophilic esophagitis (EE) is an emerging disorder with poorly understood pathogenesis. Objective Whereas prior studies have primarily focused on the role of eosinophils in disease ...diagnosis and pathogenesis, this study investigates the involvement of mast cells. Methods Total and degranulated mast cell counts were correlated to microarray and RT-PCR data to generate transcriptome expression profiles related to mast cell number and degranulation in patients with EE and healthy control subjects. Results Esophageal mastocytosis and mast cell degranulation were readily apparent in patients with EE compared with control subjects ( P < .01), as assessed by staining for total mast cells and the presence of extracellular mast cell tryptase ( P < .01). Microarray analysis revealed that mast cell levels correlated with the dysregulation of 0.8% (301 genes) of the genome, which was partially distinct from the genes that correlated with tissue eosinophilia. The expression of transcripts for the mast cell proteases carboxypeptidase A3 and tryptase, but not chymase, correlated with mast cell levels and distinguished patients with EE from control subjects. Suprabasilar mast cell counts ( P < .01) and degranulation ( P < .01) were proportional with KIT ligand mRNA expression. Treatment of patients with EE with swallowed fluticasone propionate normalized levels of mast cells and the mast cell–related transcriptome in responder patients. Conclusion Herein we have identified local mastocytosis and mast cell degranulation in the esophagi of patients with EE; identified an esophageal mast cell–associated transcriptome that is significantly divergent from the eosinophil-associated transcriptome, with carboxypeptidase A3 mRNA levels serving as the best mast cell surrogate marker; and provided evidence for the involvement of KIT ligand in the pathogenesis of EE.
Plant polysaccharides represent a virtually unlimited feedstock for the generation of biofuels and other commodities. However, the extraordinary recalcitrance of plant polysaccharides toward ...breakdown necessitates a continued search for enzymes that degrade these materials efficiently under defined conditions. Activity-based protein profiling provides a route for the functional discovery of such enzymes in complex mixtures and under industrially relevant conditions. Here, we show the detection and identification of β-xylosidases and endo-β-1,4-xylanases in the secretomes of Aspergillus niger, by the use of chemical probes inspired by the β-glucosidase inhibitor cyclophellitol. Furthermore, we demonstrate the use of these activity-based probes (ABPs) to assess enzyme–substrate specificities, thermal stabilities, and other biotechnologically relevant parameters. Our experiments highlight the utility of ABPs as promising tools for the discovery of relevant enzymes useful for biomass breakdown.
Human diploid fibroblasts undergo a limited number of population doublings in vitro and are used widely as a model of cellular aging. Despite growing evidence that cellular aging occurs as a ...consequence of altered gene expression, little is known about the activity of transcription factors in aging cells. Here, we report a dramatic reduction in the ability of proteins extracted from the nuclei of near-senescent fibroblasts to bind the serum response element which is necessary for serum-induced transcription of the c-fos gene. In contrast, the activities of proteins binding to the RNA polymerase core element, TATA, as well as to the cyclic AMP response element were maintained during cellular aging. While no major differences in the expression of the serum response factor (SRF) that binds the serum response element were seen between early-passage and late-passage cells, hyperphosphorylation of SRF was observed in near-senescent cells. Furthermore, removal of phosphatase inhibitors during the isolation of endogenous nuclear proteins restored the ability of SRF isolated from old cells to bind the SRE. These data, therefore, indicate that hyperphosphorylation of SRF plays a role in altering the ability of this protein to bind to DNA and regulate gene expression in senescent cells.
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