Comparative Analysis of Deoxynivalenol Biosynthesis Related Gene Expression among Different Chemotypes of Fusarium graminearum in Spring Wheat

Fusarium mycotoxins, deoxynivalenol (DON) and nivalenol (NIV) act as virulence factors and are essential for symptom development after initial infection in wheat. To date, 16 genes have been identified in the deoxynivalenol biosynthesis pathway. However, a comparative gene expression analysis in different chemotypes of F. graminearum in response to fusarium head blight (FHB) infection remains to be explored. Therefore, in this study, nine genes that involved in trichothecene biosynthesis were analysed among 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON) and nivalenol (NIV) producing F. graminearum strains in a time course study. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed that the expression of all examined TRI gene transcripts initiated at two days post-inoculation (dpi), peaked at three to four dpi and gradually decreased at seven dpi. The early induction of TRI genes indicates that presence of high levels of TRI gene transcripts at early stages, is important to initiate the biosynthetic pathway of DON and NIV. Comparison of gene expression among the three chemotypes showed that relative expression of TRI genes was higher in 3-ADON producing strains compared with 15-ADON and NIV strains. Comparatively higher levels of gene expression may contribute to the higher levels of DON produced by 3-ADON strains in infected grains

The use of hand-held computers (PDAs) to audit and validate eradication of a post-border detection of Khapra Beetle, Trogoderma granarium, in Western Australia

Most of Australia’s agricultural produce is exported. Demonstrating freedom from certain plant and animal pests and diseases is critical to securing and maintaining market access. Surveillance is an important tool in gaining market access and accordingly exporting countries now need to provide accurate, credible evidence to confirm pest freedom status.In the past nearly all field-collected surveillance information was recorded manually to paper reducing the rate of capture, integrity, conformity as well as security of the data. This paper describes the development of pest surveillance data collection software and hardware using PDAs (Personal Digital Assistants) to provide auditing, validation, chain of evidence and increase the volume of data collected as well as its integrity through relational databases and seamless data transfer to corporate systems. The system’s first deployment was during a T. granarium eradication. The khapra beetle (Trogoderma granarium) is one of the most serious pests of stored grain and is a regulated quarantine pest in most countries around the world. In April 2007, there was a post-border detection of T. granarium larvae and adults in a Western Australian residence. Immediate and uncompromising action was taken to quarantine the home and fumigate it with methyl-bromide at an internationally established rate known to control T. granarium (AQIS T9056). A two-year T. granarium trapping program was undertaken which used PDA software to provide evidence of complete eradication via 1273 trap inspections. This achievement was supported by GPSlocated traps, digital voice navigation itineraries, digital time and date stamps, field printed barcode labels, site imagery, all in a single hand-held unit. Keywords: T. granarium, Khapra beetle, Eradication, Biosecurity, PDA, Surveillanc

Calpain cleavage of Junctophilin-2 generates a spectrum of calcium-dependent cleavage products and DNA-rich NT1-fragment domains in cardiomyocytes

Calpains are calcium-activated neutral proteases involved in the regulation of key signaling pathways. Junctophilin-2 (JP2) is a Calpain-specific proteolytic target and essential structural protein inside Ca2+ release units required for excitation-contraction coupling in cardiomyocytes. While downregulation of JP2 by Calpain cleavage in heart failure has been reported, the precise molecular identity of the Calpain cleavage sites and the (patho-)physiological roles of the JP2 proteolytic products remain controversial. We systematically analyzed the JP2 cleavage fragments as function of Calpain-1 versus Calpain-2 proteolytic activities, revealing that both Calpain isoforms preferentially cleave mouse JP2 at R565, but subsequently at three additional secondary Calpain cleavage sites. Moreover, we identified the Calpain-specific primary cleavage products for the first time in human iPSC-derived cardiomyocytes. Knockout of RyR2 in hiPSC-cardiomyocytes destabilized JP2 resulting in an increase of the Calpain-specific cleavage fragments. The primary N-terminal cleavage product NT1 accumulated in the nucleus of mouse and human cardiomyocytes in a Ca2+-dependent manner, closely associated with euchromatic chromosomal regions, where NT1 is proposed to function as a cardio-protective transcriptional regulator in heart failure. Taken together, our data suggest that stabilizing NT1 by preventing secondary cleavage events by Calpain and other proteases could be an important therapeutic target for future studies

Do migrant remittances promote human capital formation? Evidence from 89 developing countries

The few published empirical studies on the effect of migrant remittances on educational attainments are roughly based on cross-sectional microdata from household surveys. This paper applies the generalised method of moments (GMM) estimator on aggregate level data from 1970 to 2010 in five-year intervals to examine the impact of migrant remittances on human capital formation in 89 developing countries. The estimation results show that, on average, an increase in migrant remittance inflows by 1% is associated with a 2% rise in years of schooling at both the secondary and tertiary levels. This suggests that migrant remittances have the potential to relax liquidity constraints and generate spillover effects that facilitate more schooling opportunities in remittance-receiving countries

The Value of Rare Genetic Variation in the Prediction of Common Obesity in European Ancestry Populations

Polygenic risk scores (PRSs) aggregate the effects of genetic variants across the genome and are used to predict risk of complex diseases, such as obesity. Current PRSs only include common variants (minor allele frequency (MAF) ≥1%), whereas the contribution of rare variants in PRSs to predict disease remains unknown. Here, we examine whether augmenting the standard common variant PRS (PRScommon) with a rare variant PRS (PRSrare) improves prediction of obesity. We used genome-wide genotyped and imputed data on 451,145 European-ancestry participants of the UK Biobank, as well as whole exome sequencing (WES) data on 184,385 participants. We performed single variant analyses (for both common and rare variants) and gene-based analyses (for rare variants) for association with BMI (kg/m2), obesity (BMI ≥ 30 kg/m2), and extreme obesity (BMI ≥ 40 kg/m2). We built PRSscommon and PRSsrare using a range of methods (Clumping+Thresholding [C+T], PRS-CS, lassosum, gene-burden test). We selected the best-performing PRSs and assessed their performance in 36,757 European-ancestry unrelated participants with whole genome sequencing (WGS) data from the Trans-Omics for Precision Medicine (TOPMed) program. The best-performing PRScommon explained 10.1% of variation in BMI, and 18.3% and 22.5% of the susceptibility to obesity and extreme obesity, respectively, whereas the best-performing PRSrare explained 1.49%, and 2.97% and 3.68%, respectively. The PRSrare was associated with an increased risk of obesity and extreme obesity (ORobesity = 1.37 per SDPRS, P obesity = 1.7x10-85; ORextremeobesity = 1.55 per SDPRS, P extremeobesity = 3.8x10-40), which was attenuated, after adjusting for PRScommon (ORobesity = 1.08 per SDPRS, P obesity = 9.8x10-6; ORextremeobesity= 1.09 per SDPRS, P extremeobesity = 0.02). When PRSrare and PRScommon are combined, the increase in explained variance attributed to PRSrare was small (incremental Nagelkerke R2 = 0.24% for obesity and 0.51% for extreme obesity). Consistently, combining PRSrare to PRScommon provided little improvement to the prediction of obesity (PRSrare AUC = 0.591; PRScommon AUC = 0.708; PRScombined AUC = 0.710). In summary, while rare variants show convincing association with BMI, obesity and extreme obesity, the PRSrare provides limited improvement over PRScommon in the prediction of obesity risk, based on these large populations

Author Correction: Organic osmolytes preserve the function of the developing tight junction in ultraviolet B-irradiated rat epidermal keratinocytes

From Springer Nature via Jisc Publications RouterHistory: registration 2020-05-06, pub-electronic 2020-05-20, online 2020-05-20, collection 2020-12Publication status: PublishedAn amendment to this paper has been published and can be accessed via a link at the top of the paper

Bronchoalveolar Lavage Lymphocytes in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease: A Systematic Review

RATIONALE: Hypersensitivity Pneumonitis (HP) is an interstitial lung disease (ILD) characterized by inflammation and/or fibrosis in response to an inhalational exposure. OBJECTIVE: To determine the value of bronchoalveolar lavage (BAL) fluid lymphocyte cellular analysis in the detection of HP among patients with newly detected ILD. METHODS: This systematic review was undertaken in the context of development of an American Thoracic Society (ATS), Japanese Respiratory Society (JRS), and Asociación Latinoamericana del Tórax (ALAT) clinical practice guideline. The clinical question was, should patients with newly detected ILD undergo BAL fluid lymphocyte analysis to diagnose HP? Medline, Embase, and grey literature were searched through October 2019. Studies that reported the percentage of BAL fluid lymphocytes for various ILDs were selected for inclusion. Meta-analyses compared the mean percentage of BAL fluid lymphocytes among patients with HP to that among patients with Idiopathic Pulmonary Fibrosis (IPF) or sarcoidosis. The sensitivity and specificity by which various percentages of BAL fluid lymphocytes distinguish HP from IPF and sarcoidosis were also evaluated. RESULTS: Eighty-four articles were selected. No randomized trials or observational studies were identified that compared BAL fluid lymphocyte analysis to no BAL fluid lymphocyte analysis in patients with ILD. Included studies were case series describing BAL fluid cell differentials in patients with various ILDs. The percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared to IPF. Similarly, the percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared to sarcoidosis. A threshold of 20% BAL fluid lymphocytes distinguished fibrotic HP from IPF with a sensitivity and specificity of 69% and 61% respectively, and nonfibrotic HP from IPF with a sensitivity and specificity of 95% and 61% respectively. It distinguished fibrotic HP from sarcoidosis with a sensitivity and specificity of 69% and 26% respectively, and nonfibrotic HP from sarcoidosis with a sensitivity and specificity of 95% and 26% respectively. CONCLUSION: The percentage of BAL fluid lymphocytes is higher in HP than IPF or sarcoidosis. However, a threshold that distinguishes HP from IPF or sarcoidosis with both high sensitivity and high specificity was not identified

Androgen-dependent apoptosis in male germ cells is regulated through the proto-oncoprotein Cbl

The proto-oncoprotein Cbl is known to control several signaling processes. It is highly expressed in the testis, and because spermatogenesis is androgen dependent, we investigated the androgen dependency expression of Cbl through its testicular sublocalization and its expression levels in rats that were exposed to the antiandrogen flutamide or were hypophysectomized. We report the androgen dependency of Cbl as it localizes in pachytene spermatocytes during androgen-dependent stages, is down-regulated upon flutamide exposure, and is up-regulated with testosterone in hypophysectomized rats. Coculture experiments showed the key control exerted by the Sertoli cell on Cbl activity. As flutamide induces germ cell apoptosis, we investigate members of the Bcl-2 family upon flutamide exposure. We show that the proapoptotic Bcl-2 family member Bim mirrored Cbl expression through a posttranscriptional process. We also show that in Cbl knockout mouse testes, the imbalance between the high expression of Bim and Smac/Diablo and antiapoptotic factors such as cellular inhibitor of apoptosis 2 favors a survival process, which makes these mice unresponsive to androgen withdrawal and could explain their hypofertility