Characterization of Lasiodiplodia theobromae and L. pseudotheobromae causing fruit rot on pre-harvest mango in Malaysia

Lasiodiplodia species are important plant pathogens in mango production countries, infecting plants during both pre- and post- harvest phases. Fruit rot reduces mango production and creates tremendous losses in economy of the involved countries. Fungal isolation was conducted in eight locations throughout Peninsular Malaysia. Species identification was based on morphological characterisation and internal transcribed spacer (ITS) and β-tubulin (BT2) gene sequences analysis. Twenty isolates were obtained and identified as Lasiodiplodia theobromae (17isolates) and L. pseudotheobromae (3 isolates). Phylogenetic analysis using maximum-likelihood method demonstrated that all isolates of L. theobromae and L. pseudotheobromae formed a monophyletic clade. In pathogenicity tests, most fungal isolates inoculated on mango fruit showed fruit rot symptom. The most virulent isolate was L. theobromae A1718 with disease severity index (DSI)of 87.5%

The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability

In multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral essential amino acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells matured, expression of the amino acid transporter gene Lat3 increased, which increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi-mediated knockdown of LAT3 triggered a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells through the mTORC1 (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation initiation factor 4E–binding protein) pathway. CRISPR-mediated deletion of members of the 4E-BP family in murine erythroid cells rendered them resistant to mTORC1 and LAT3 inhibition and restored hemoglobin production. These results identify a developmental role for LAT3 in red blood cells and demonstrate that mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the translational level to sufficient uptake of NEAAs, particularly L-leucine.National Institutes of Health (U.S.) (P01 HL032262

Surveillance of Airborne Adenovirus and Mycoplasma pneumoniae in a Hospital Pediatric Department

This investigation evaluated the distributions of airborne adenovirus and Mycoplasma pneumoniae in public areas in the pediatric department of Children's Hospital in northern Taiwan. The airborne viral and bacterial concentrations were evaluated twice a week for a year using filter sampling with an airflow rate of 12 liters per minute for eight hours in the pediatric outpatient department and 24 hours in the pediatric emergency room. Real-time polymerase chain reaction assays were conducted for analysis. Approximately 18% of the air samples from the pediatric emergency room were found to contain adenovirus. Approximately forty-six percent of the air samples from the pediatric outpatient department contained Mycoplasma pneumoniae DNA products. High detection rates of airborne adenovirus DNA were obtained in July and August in the pediatric public areas. Airborne Mycoplasma pneumoniae was detected only in July in the pediatric emergency room and the peak levels were found from August to January in the pediatric outpatient department. Airborne particles that contained adenovirus and Mycoplasma pneumoniae were the most prevalent in the pediatric public areas. The potential relationship between these airborne viral/bacterial particles and human infection should be examined further

Bioencapsulation and Colonization Characteristics of Lactococcus lactis subsp. lactis CF4MRS in Artemia franciscana: a Biological Approach for the Control of Edwardsiellosis in Larviculture

Predominance of beneficial bacteria helps to establish a healthy microbiota in fish gastrointestinal system and thus to reduce emerging pathogen. In this study, the colonization efficacy of Lactococcus lactis subsp. lactis CF4MRS in Artemia franciscana and its potential as a probiotic in suppressing Edwardsiella sp. infection were investigated in vivo. The colonization extent of the bioencapsulated L. lactis was established through visualization of gfp gene-transformed L. lactis in A. franciscana. Here, we demonstrate that when A. franciscana is administrated with L. lactis at 108 CFU mL−1 for 8 h, the highest relative percentage of survival (RPS = 50.0) is observed after inoculation with Edwardsiella sp. The total counts of L. lactis entrapped in Artemia were the highest (ranged from 3.2 to 5.1 × 108 CFU mL−1), when 108–109 CFU mL−1 of L. lactis was used as starting inoculum, with the bioencapsulation performed within 8–24 h. Fluorescent microscopy showed gfp-transformed L. lactis colonized the external trunk surfaces, mid-gut and locomotion antennules of the A. franciscana nauplii. These illustrations elucidate the efficiency of colonization of L. lactis in the gastrointestinal tract and on the body surfaces of Artemia. In conclusion, L. lactis subsp. lactis CF4MRS shows a good efficacy of colonization in Artemia and has the potential for biocontrol/probiotic activity against Edwardsiella sp. infection

Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race

Women of African ancestry suffer higher rates of breast cancer mortality compared with all other groups in the United States. Though the precise reasons for these disparities remain unclear, many recent studies have implicated a role for differences in tumor biology. Using an epitope-validated antibody against the endoplasmic reticulum-associated E3 ligase, gp78, we show that elevated levels of gp78 in patient breast cancer cells predict poor survival. Moreover, high levels of gp78 are associated with poor outcomes in both ER+ and ER- tumors, and breast cancers expressing elevated amounts of gp78 protein are enriched in gene expression pathways that influence cell cycle, metabolism, receptor-mediated signaling, and cell stress response pathways. In multivariate analysis adjusted for subtype and grade, gp78 protein is an independent predictor of poor outcomes in women of African ancestry. Furthermore, gene expression signatures, derived from patients stratified by gp78 protein expression, are strong predictors of recurrence and pathological complete response in retrospective clinical trial data and share many common features with gene sets previously identified to be overrepresented in breast cancers based on race. These findings implicate a prominent role for gp78 in tumor progression and offer insights into our understanding of racial differences in breast cancer outcomes.Fil: Singhal, Sandeep K.. No especifíca;Fil: Byun, Jung S.. National Institutes of Health; Estados UnidosFil: Yan, Tingfen. National Institutes of Health; Estados UnidosFil: Yancey, Ryan. Columbia University; Estados UnidosFil: Caban, Ambar. Columbia University; Estados UnidosFil: Hernandez, Sara Gil. National Institutes of Health; Estados UnidosFil: Bufford, Sediqua. No especifíca;Fil: Hewitt, Stephen M.. No especifíca;Fil: Winfield, Joy. Columbia University; Estados UnidosFil: Pradhan, Jaya. Columbia University; Estados UnidosFil: Mustkov, Vesco. Columbia University; Estados UnidosFil: McDonald, Jasmine A.. No especifíca;Fil: Pérez Stable, Eliseo J.. National Institutes of Health; Estados UnidosFil: Nápoles, Anna María. National Institutes of Health; Estados UnidosFil: Vohra, Nasreen. No especifíca;Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Yates, Clayton. No especifíca;Fil: Davis, Melissa B.. No especifíca;Fil: Yang, Mei. No especifíca;Fil: Tsai, Yien Che. No especifíca;Fil: Weissman, Allan M.. No especifíca;Fil: Gardner, Kevin. Columbia University; Estados Unido

Molecular Analysis of Repeated Methicillin-Resistant Staphylococcus aureus Infections in Children

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen that causes severe morbidity and mortality in hospitalized patients. It is unclear whether repeated MRSA infections in pediatric patients are caused by relapse of previous infecting strains or by acquiring new strains from extrinsic sources. The study aimed to define the genetic relatedness of MRSA isolates from children with repeated infections. METHODOLOGY/PRINCIPAL FINDINGS: Children with multiple MRSA infections during 2004-2006 were identified in a teaching hospital. Repeated infections were confirmed by chart review and the responsible isolates were genotyped and screened for Panton-Valentine leukocidin (PVL) genes. Two consecutive episodes comprised an infection pair, and strain relatedness was defined for each pair as indistinguishable, highly related, or distinct if the isolates were of the same subtype, the same genotype, or different genotype, respectively. A total of 114 episodes comprising 66 infection pairs were identified in 48 children. The interval of infection pairs ranged from 15 days to 346 days, with a median duration of 57.5 days. Genotypings classified all isolates into 7 genotypes and 31 subtypes. Of 66 pairs, 46 (69.7%), 13 (19.7%) and 7 (10.6%) pairs were caused by indistinguishable, highly related and distinct strains, respectively. Subsequent infections caused by indistinguishable strains were more common for PVL-positive strains (17/18, 94.4%) than for PVL-negative strains (29/48, 60.4%, P = 0.007). The strain relatedness was not affected by the durations of interval between infections. CONCLUSIONS/SIGNIFICANCE: Most repeated MRSA infections in children are caused by indistinguishable strains even after a long period of interval, suggesting that persistent carriage and relapse of initial infecting strains were responsible for the majority of recurrent MRSA infections

Ubiquitylation in ERAD: Reversing to Go Forward?

Proteins are co-translationally inserted into the endoplasmic reticulum (ER) where they undergo maturation. Homeostasis in the ER requires a highly sensitive and selective means of quality control. This occurs through ER-associated degradation (ERAD).This complex ubiquitin-proteasome–mediated process involves ubiquitin conjugating enzymes (E2) and ubiquitin ligases (E3),lumenal and cytosolic chaperones, and other proteins, including the AAA ATPase p97 (VCP; Cdc48 in yeast). Probing of processes involving proteasomal degradation has generally depended on proteasome inhibitors or knockdown of specific E2s or E3s. In this issue of PLoS Biology, Ernst et al. demonstrate the utility of expressing the catalytic domain of a viral deubiquitylating enzyme to probe the ubiquitin system. Convincing evidence is provided that deubiquitylation is integral to dislocation of ERAD substrates from the ER membrane. The implications of this work for understanding ERAD and the potential of expressing deubiquitylating enzyme domains for studying ubiquitin-mediated processes are discussed

The epidemiology and survival of extrapulmonary small cell carcinoma in South East England, 1970–2004

<p>Abstract</p> <p>Background</p> <p>Extrapulmonary small cell carcinoma (EPSCC) is a rare cancer and few studies describe its epidemiology. Our objectives were to compare the incidence and survival of EPSCC in South East England with small cell carcinoma of the lung (SCLC), to determine the most common anatomical presenting sites for EPSCC and to compare survival in EPSCC by disease stage and site of diagnosis.</p> <p>Methods</p> <p>We used data from the Thames Cancer Registry database for South East England between 1970 and 2004 to determine the incidence, most common anatomical sites, and survival by site, and stage of EPSCC. 1618 patients registered with EPSCC were identified. We calculated the age-standardised incidence rate for EPSCC using the European standard population and compared this to that for SCLC. We calculated survival using the Kaplan-Meier method for EPSCC and SCLC, and reported 3-year survival for different EPSCC anatomical sites and disease stages.</p> <p>Results</p> <p>The incidence of EPSCC was much lower than for SCLC, similar in males and females, and stable throughout the study period, with incidence rates of 0.45 per 100,000 in males and 0.37 in females during 2000–2004. In general, patients with EPSCC had a better 3-year survival (19%) than SCLC (5%). The most common anatomical sites for EPSCC were oesophagus (18%), other gastrointestinal (15%), genitourinary (20%), head and neck (11%), and breast (10%). Breast EPSCC had the best 3-year survival (60%) and gastrointestinal EPSCC the worst (7%).</p> <p>Conclusion</p> <p>This study suggests that EPSCC has a stable incidence and confirms that it presents widely, but most commonly in the oesophagus and breast. Site and extent of disease influence survival, with breast EPSCC having the best prognosis. Further studies using standardised diagnosis, prospective case registers for uncommon diseases and European cancer registries are needed to understand this disease.</p

Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1-mutant myelodysplastic syndromes.

The splicing factor SF3B1 is the most frequently mutated gene in myelodysplastic syndromes (MDS), and is strongly associated with the presence of ring sideroblasts (RS). We have performed a systematic analysis of cryptic splicing abnormalities from RNA sequencing data on hematopoietic stem cells (HSCs) of SF3B1-mutant MDS cases with RS. Aberrant splicing events in many downstream target genes were identified and cryptic 3' splice site usage was a frequent event in SF3B1-mutant MDS. The iron transporter ABCB7 is a well-recognized candidate gene showing marked downregulation in MDS with RS. Our analysis unveiled aberrant ABCB7 splicing, due to usage of an alternative 3' splice site in MDS patient samples, giving rise to a premature termination codon in the ABCB7 mRNA. Treatment of cultured SF3B1-mutant MDS erythroblasts and a CRISPR/Cas9-generated SF3B1-mutant cell line with the nonsense-mediated decay (NMD) inhibitor cycloheximide showed that the aberrantly spliced ABCB7 transcript is targeted by NMD. We describe cryptic splicing events in the HSCs of SF3B1-mutant MDS, and our data support a model in which NMD-induced downregulation of the iron exporter ABCB7 mRNA transcript resulting from aberrant splicing caused by mutant SF3B1 underlies the increased mitochondrial iron accumulation found in MDS patients with RS