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Heat shock response (HSR) is a universal mechanism in all organisms. It is under tight regulation by heat shock factors (HSFs) and heat shock proteins (HSPs) after heat shock (HS) to prevent stress damage. On the attenuation of HSR, HSP70 and HSF Binding Protein1 (HSBP1) interact with HSF1 and thus dissociate trimeric HSF1 into an inert monomeric form in humans. However, little is known about the effect of HSBP with thermal stress in plants. This report describes our investigation of the role of AtHSBP in Arabidopsis (Arabidopsis thaliana) by genetic and molecular approaches. AtHSBP was heat inducible and ubiquitously expressed in all tissues; AtHSBP was also crucial for seed development, as demonstrated by AtHSBP-knockout lines showing seed abortion. Thermotolerance results showed that AtHSBP participates in acquired thermotolerance but not basal thermotolerance and is a negative regulator of HSR. Subcellular localization revealed that the cytosol-localized AtHSBP translocated to the nucleus in response to HS. Protoplast two-hybrid assay results confirmed that AtHSBP interacts with itself and with the HSFs, AtHSFA1a, AtHSFA1b, and AtHSFA2. AtHSBP also negatively affected AtHSFA1b DNA-binding capacity in vitro. Quantitative polymerase chain reaction and western-blot analysis demonstrated that altered levels of AtHSBP lead to differential HSP expression, mainly during the recovery from HS. These studies provide a new insight into HSBP in plants and reveal that AtHSBP is a negative regulator of HSR and required for seed development.

Background Persistent Pseudomonas aeruginosa (PPA) infection promotes lung function deterioration in children with cystic fibrosis (CF). Although early CF diagnosis through newborn screening (NBS) has been shown to provide nutritional/growth benefit, it is unclear whether NBS lowers the risk of PPA infection and how the effect of NBS vary with age. Modeling the onset age of PPA infection is challenging because 1) the onset age of PPA infection is interval censored in patient registry data; and 2) some risk factors such as NBS may have time-varying effects. Methods This problem fits into the framework of a recently developed Bayesian dynamic Cox model for interval censored data, where each regression coefficient is allowed to be time-varying to an extent determined by the data. Results Application of the methodology to data from the CF Foundation Patient Registry revealed interesting findings. Compared with patients with meconium ileus or diagnosed through signs or symptoms, patients diagnosed through NBS had significantly lower risks of acquiring PPA infection between age 1 and 2 years, and the benefit in survival rate was found to last up to age 4 years. Two cohorts of five years apart were compared. Patients born in cohort 2003–2004 had significantly lower risks of the PPA infections at any age up to 4 years than those born in 1998–1999. Conclusions The study supports benefits of NBS on PPA infection in early childhood. In addition, our analyses demonstrate that patients in the more recent cohort had significantly lower risks of acquiring PPA infection up to age 4 years, which suggests improved CF treatment and care over time.

Abstract Although early diagnosis of cystic fibrosis (CF) can lead to nutritional benefits, there has been uncertainty about pulmonary outcomes. Using a randomized controlled trial with unique unblinding/surveillance, we evaluated patients with CF who received similar treatment after being assigned to an early diagnosis (screened) group or to a standard diagnosis (control) group. When the youngest patient was 7 years of age, we compared outcomes using pulmonary function data and quantitative chest radiology. In the screened group (56 patients), diagnosis was made at a younger age of 12.4 weeks, compared with the diagnosis in control group (47 control patients) at the age of 95.8 weeks, but included a significantly greater proportion of patients with ΔF508 genotypes and pancreatic insufficiency. The first chest radiograph showed significantly fewer abnormalities in the screened group; but, over time, the two groups converged, and after 10 years of age the screened patients showed worse chest X-ray scores associated with earlier acquisition of Pseudomonas aeruginosa. No differences were detected in any measure of pulmonary dysfunction, which was generally mild in each group. Although CF neonatal screening provides a potential opportunity for better pulmonary outcomes, it appears that respiratory infections and pancreatic status are the dominant factors in pulmonary prognosis.

Glucocorticoids are administered to patients with cystic fibrosis for acute indications, such as bronchiolitis, 1 bronchial hyperreactivity, 2 and allergic bronchopulmonary aspergillosis, 3 as well as for long-term treatment of mild-to-moderate obstructive pulmonary disease, to reduce inflammation and improve lung function. 4 – 9 In two randomized clinical trials, patients with cystic fibrosis and mild-to-moderate lung disease who were treated with 1 or 2 mg of prednisone per kilogram of body weight on an alternate-day schedule over a period of two to four years had significantly better pulmonary function than such patients who were given placebo. 5 , 6 The benefits of long-term treatment with glucocorticoids in . . .

Recurrent events data are frequently encountered in biomedical follow-up studies. The generalized accelerated recurrence time (GART) model (Sun et al., 2016), which formulates covariate effects on the time scale of the mean function of recurrent events (i.e., time to expected frequency), has arisen as a useful secondary analysis tool to provide meaningful physical interpretations. In this article, we investigate the GART model in a multivariate recurrent events setting, where subjects may experience multiple types of recurrent events and some event types may be missing. We propose methods for the GART model that utilize the inverse probability weighting technique or the estimating equation projection strategy to handle event types that are missing at random. The new methods do not require imposing any parametric model for the missing mechanism, and thus are robust; moreover, they enjoy easy and stable implementation. We establish the uniform consistency and weak convergence of the resulting estimators and develop appropriate inferential procedures. Extensive simulation studies and an application to a dataset from Cystic Fibrosis Foundation Patient Registry (CFFPR) illustrate the validity and practical utility of the proposed methods.

In survival analysis, quantile regression has become a useful approach to account for covariate effects on the distribution of an event time of interest. In this article, we discuss how quantile regression can be extended to model counting processes and thus lead to a broader regression framework for survival data. We specifically investigate the proposed modeling of counting processes for recurrent events data. We show that the new recurrent events model retains the desirable features of quantile regression such as easy interpretation and good model flexibility, while accommodating various observation schemes encountered in observational studies. We develop a general theoretical and inferential framework for the new counting process model, which unifies with an existing method for censored quantile regression. As another useful contribution of this work, we propose a sample-based covariance estimation procedure, which provides a useful complement to the prevailing bootstrapping approach. We demonstrate the utility of our proposals via simulation studies and an application to a dataset from the U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR). Supplementary materials for this article are available online.

Heat shock response (HSR) is a universal mechanism in all organisms. It is under tight regulation by heat shock factors (HSFs) and heat shock proteins (HSPs) after heat shock (HS) to prevent stress damage. On the attenuation of HSR, HSP70 and HSF Binding Protein1 (HSBP1) interact with HSF1 and thus dissociate trimeric HSF1 into an inert monomeric form in humans. However, little is known about the effect of HSBP with thermal stress in plants. This report describes our investigation of the role of AtHSBP in Arabidopsis (Arabidopsis thaliana) by genetic and molecular approaches. AtHSBP was heat inducible and ubiquitously expressed in all tissues; AtHSBP was also crucial for seed development, as demonstrated by AtHSBP-knockout lines showing seed abortion. Thermotolerance results showed that AtHSBP participates in acquired thermotolerance but not basal thermotolerance and is a negative regulator of HSR. Subcellular localization revealed that the cytosol-localized AtHSBP translocated to the nucleus in response to HS. Protoplast two-hybrid assay results confirmed that AtHSBP interacts with itself and with the HSFs, AtHSFA1a, AtHSFA1b, and AtHSFA2. AtHSBP also negatively affected AtHSFA1b DNA-binding capacity in vitro. Quantitative polymerase chain reaction and western-blot analysis demonstrated that altered levels of AtHSBP lead to differential HSP expression, mainly during the recovery from HS. These studies provide a new insight into HSBP in plants and reveal that AtHSBP is a negative regulator of HSR and required for seed development.

The effect of different dietary saturated fats on postprandial lipid metabolism is unclear. We compared fasting and postprandial lipid responses in rats fed polyunsaturated corn oil or one of four saturated fats: palm oil, intact butterfat, a liquid butterfat fraction enriched in 18:1 and a solid butterfat fraction enriched in 16:0 and 18:0. Rats were adapted to eat a daily 3-hr meal containing 16% fat (w/w) and 0.017-0.048% cholesterol for 3-4 weeks. Postprandial lipemic responses were determined by measuring (1) plasma cholesterol, triacylglycerol (TAG), free glycerol and insulin levels, (2) postheparin plasma lipoprotein lipase (PHLPL) activity, (3) TAG content remaining in the gastrointestinal tract, and (4) lymph chylomicron secretion rates. Ingestion of corn oil, compared to all four saturated fats, resulted in (1) significantly lower fasting and postprandial plasma TAG and cholesterol levels and 50-100% less TAG accumulation (mM/24 hr), (2) higher PHLPL activities (0-9 hr), free glycerol (2.5-4.5 hr) and insulin (2.5 hr) levels, and (3) no differences in lymph chylomicron TAG or cholesterol output (mg/24 hr). This suggests that increased clearance was responsible for the reduced postprandial lipemia noted with corn oil. Ingestion of palm oil, liquid and solid butterfat resulted in similar postprandial plasma TAG levels and chylomicron TAG secretion rates. However, significantly higher PHLPL activities (0-9 hr) were noted with ingestion of palm oil compared to liquid or solid butterfat and larger chylomicron size was noted with infusion of liquid compared to solid butterfat. This suggests that postprandial lipid metabolism differed with palm oil, liquid and solid butterfats despite similar absorption. Analyses of fatty acid and TAG profiles (total acyl carbon number or Cn) demonstrated that short chain fatty acids (4:0 and 6:0) and small TAG molecules (C $\\sb{30}$ -C $\\sb{34}$ ) of the liquid and solid butterfats were preferentially hydrolyzed by gastric lipolysis and did not appear in lymph chylomicrons. In conclusion, ingestion of corn oil resulted in reduced postprandial lipemia compared to saturated fats, however, each saturated fat demonstrated an unique effect on postprandial lipid metabolism. Differences in fatty acid and TAG profiles may contribute to the differential postprandial lipemic responses noted in these studies.

This study proposed that transformational leaders use various behaviors to provoke followers’ organizationally beneficial behaviors (e.g., better task performance and helping behaviors) through ignition of followers’ work engagement. That is, employees who inspired by transformational leadership are more likely to immerse themselves in the work, and, in turn, this is likely to result in better task performance and helping behaviors. In this study, we adopted a multitemporal and multisource research design to reduce the consideration of common method variance. Hypotheses were tested on a sample of 507 nurses working in 44 teams. The hierarchical linear regression analysis showed that, after controlling for several relevant variables (e.g., leader–member exchange [LMX], role-based self-efficacy, and transactional leadership) and several participants’ demographic variables (e.g., gender, age, and education), work engagement still mediates the positive relationship among transformational leadership, job performance, and helping behavior. Strengths, limitations, practical implications, and directions for future research are discussed.