Nonsense-mediated mRNA decay (NMD) plays an important role in eukaryotic gene expression, yet the scope and the defining features of NMD-targeted transcripts remain elusive. To address these issues, we reevaluated the genome-wide expression of annotated transcripts in yeast cells harboring deletions of the UPF1, UPF2, or UPF3 genes. Our new RNA-seq analyses confirm previous results of microarray studies, but also uncover hundreds of new NMD-regulated transcripts that had escaped previous detection, including many intron-containing pre-mRNAs and several noncoding RNAs. The vast majority of NMD-regulated transcripts are normal-looking protein-coding mRNAs. Our bioinformatics analyses reveal that this set of NMD-regulated transcripts generally have lower translational efficiency and higher ratios of out-of-frame translation. NMD-regulated transcripts also have lower average codon optimality scores and higher transition probability to nonoptimal codons. Collectively, our results generate a comprehensive catalog of yeast NMD substrates and yield new insights into the mechanisms by which these transcripts are targeted by NMD.

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In a cross-sectional assessment using self-report measures, we found that nearly a third of first year residents prior to starting their internships experience burnout. They exhibit lower levels of mindfulness and coping skills and higher levels of depression symptoms, fatigue, worry, and stress. These preliminary findings should encourage programs to initiate and study curricula that combine mindfulness and self-awareness coping strategies to enhance or protect against burnout as well as cognitive behavioral coaching strategies to offset symptoms of burnout when present.

The Dcp1-Dcp2 decapping enzyme and the decapping activators Pat1, Dhh1, and Lsm1 regulate mRNA decapping, but their mechanistic integration is unknown. We analyzed the gene expression consequences of deleting PAT1, LSM1, or DHH1, or the DCP2 C-terminal domain, and found that: i) the Dcp2 C-terminal domain is an effector of both negative and positive regulation; ii) rather than being global activators of decapping, Pat1, Lsm1, and Dhh1 directly target specific subsets of yeast mRNAs and loss of the functions of each of these factors has substantial indirect consequences for genome-wide mRNA expression; and iii) transcripts targeted by Pat1, Lsm1, and Dhh1 exhibit only partial overlap, are generally translated inefficiently, and, as expected, are targeted to decapping-dependent decay. Our results define the roles of Pat1, Lsm1, and Dhh1 in decapping of general mRNAs and suggest that these factors may monitor mRNA translation and target unique features of individual mRNAs.

Background: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed.Objective: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. Methods:The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63 + basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed | 1801 DUAN et Al.

Nonsense-mediated mRNA decay (NMD) is one of three regulatory mechanisms that monitor the cytoplasm for aberrant mRNAs. NMD is usually triggered by premature translation termination codons that arise from mutations, transcription errors, or inefficient splicing, but which also occur in transcripts with alternately spliced isoforms or upstream open reading frames, or in the context of long 3′-UTRs. This surveillance pathway requires detection of the nonsense codon by the eukaryotic release factors (eRF1 and eRF3) and the activities of the Upf proteins, but the exact mechanism by which a nonsense codon is recognized as premature, and the individual roles of the Upf proteins, are poorly understood. In this review, we highlight important differences between premature and normal termination. Based on our current understanding of normal termination and ribosome recycling, we propose a similar mechanism for premature termination events that includes a role for the Upf proteins. In this model, the Upf proteins not only target the mRNA and nascent peptide for degradation, but also assume the role of recycling factors and rescue a ribosome stalled at a premature nonsense codon. The ATPase and helicase activities of Upf1, with the help of Upf2 and Upf3, are thus thought to be the catalytic force in ribosome subunit dissociation and ribosome recycling at an otherwise poorly dissociable termination event. While this model is somewhat speculative, it provides a unified vision for current data and a direction for future research.

Pilonidal sinus disease is a benign disorder with an unidentified etiology and is observed mainly in young adults. It is an important health problem because it causes work loss. Although various nonsurgical treatment options have been tried up to date, there is a consensus on surgical intervention to treat the disease today. The optimal surgical method should be simple, associated with short hospital stay and low recurrence rates. In this study, patients who have undergone different surgical treatment methods due to pilonidal disease were retrospectively analyzed. The medical records of 175 patients who were operated on between 2002 and 2005 at the General Surgery Departments of Gaziosmanpasa University Medical School and Bartin State Hospital for pilonidal disease were reviewed for treatment option, postoperative complications, hospitalization time, work-off periods, and recurrence rates. The patients consisted of 150 (85.3%) males with a mean age of 26.47 +/- 7.78 years. Marsupialization was applied to 82 (46.9%), unroofing to 20 (14.7%), primary closure to 29 (16.6%), and Limberg flap to 44 (25.1%) patients. The longest hospitalization period of 3.61 +/- 1.08 days was observed in the Limberg flap group. The longest return to work period (20.12 +/- 5.1 days) was observed in the marsupialization group. Both differences were significant. The highest complication rate was observed among the primary closure group (31%) followed by the patients treated by Limberg flap technique (15.8%). In the primary closure group, infection was detected in five (17.2%) and wound dehiscence in four (13.8%) individuals. The highest complication rates (31.03%) and recurrences (13.8%) were observed in the primary closure group. Various operative methods utilized in the treatment of pilonidal disease are associated with a number of advantages and disadvantages. Postoperative complication rates of unroofing and marsupialization are low, but require long wound care. In our study, we did not observe any recurrence among the patients treated by unroofing, but experienced a high recurrence ratio among subjects treated by marsupialization. In addition, there were high complication rates in the primary closure and Limberg flap groups. So, the best option is to explain the advantages and disadvantages of the available surgical methods and respect the patient's decision.

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