Understanding the nature of blast resistance in combined bacterial leaf blight and blast gene pyramided lines of rice variety tellahamsa.

BACKGROUND: Rice blast and bacterial leaf blight (BLB) are the most limiting factors for rice production in the world which cause yield losses typically ranging from 20 to 30% and can be as high as 50% in some areas of Asia especially India under severe infection conditions. METHODS AND RESULTS: An improved line of Tellahamsa, TH-625-491 having two BLB resistance genes (xa13 and Xa21) and two blast resistance genes (Pi54 and Pi1) with 95% Tellahamsa genome was used in the present study. TH-625-491 was validated for all four target genes and was used for backcrossing with Tellahamsa. Seventeen IBC1F1 plants heterozygous for all four target genes, 19 IBC1F2 plants homozygous for four, three and two gene combinations and 19 IBC1F2:3 plants also homozygous for four, three and two gene combinations were observed. Among seventeen IBC1F1 plants, IBC1F1-62 plant recorded highest recurrent parent genome (97.5%) covering 75 polymorphic markers. Out of the total of 920 IBC1F2 plants screened, 19 homozygous plants were homozygous for four, three and two target genes along with bacterial blight resistance. Background analysis was done in all 19 homozygous IBC1F2 plants possessing BLB resistance (possessing xa13, Xa21, Pi54 and Pi1 in different combinations) with five parental polymorphic SSR markers. IBC1F2-62-515 recovered 98.5% recurrent parent genome. The four, three and two gene pyramided lines of Tellahamsa exhibited varying resistance to blast. CONCLUSIONS: Results show that there might be presence of antagonistic effect between bacterial blight and blast resistance genes since the lines with Pi54 and Pi1 combination are showing better resistance than the combinations with both bacterial blight and blast resistance genes.

Long-Term Follow up of Blinatumomab in Older Patients with B-Cell Acute Lymphoblastic Leukemia.

Older adults who are diagnosed with acute lymphoblastic leukemia (ALL) and are treated with chemotherapy generally have poor outcomes. Blinatumomab is a CD19/CD3 bispecific T-cell engager that has been approved for the treatment of B-cell ALL in the relapsed/refractory setting or in patients with minimal residual disease (MRD) positivity. We previously reported on a small cohort of older adults with newly diagnosed Philadelphia chromosome negative B-cell ALL who were treated with blinatumomab monotherapy in the first line setting. This is a long-term follow up of those patients and their clinical courses. All five patients achieved complete remission (CR) after one cycle of blinatumomab, and three were MRD-negative. Two patients completed three cycles of blinatumomab, two patients completed four cycles of blinatumomab, and one patient completed 17 cycles of blinatumomab total. In the last four years, four of these patients had relapsed disease requiring additional therapy. Two patients are alive after 61 months and 57 months since their first cycle of blinatumomab. Two of the patients died at 10 months and one died at 20 months. Here we describe the long-term clinical courses of these patients.

Audiovestibular Dysfunction in Siblings with Charcot-Marie-Tooth Disease 4F: A Case Series.

BACKGROUND: Charcot-Marie-Tooth disease type 4F (CMT4F) is an autosomal recessive disorder with symptoms presenting in early adulthood. This clinical case series demonstrates atypical findings in cervical and ocular vestibular evoked myogenic potentials (VEMP) in siblings with CMT4F. PURPOSE: The aim of this study was to highlight the audiovestibular test findings in CMT4F. RESEARCH DESIGN: Case series study sample: 4 siblings, 3 of whom diagnosed with CMT4F. DATA COLLECTION AND ANALYSIS: Audiological test battery and electrophysiological tests comprising auditory brainstem response (ABR) and VEMP (both cervical and ocular) were performed in our patient population. RESULTS: Older siblings, in whom the hearing loss was present, manifested prolonged peak V latencies in ABR. Three out of four siblings with CMT4F showed prolongation of latencies on cervical and ocular VEMP. CONCLUSIONS: In many neurodegenerative conditions, prolongation of ABR peak latencies has often been reported in the literature. There have also been a few reports of prolonged VEMP peak latencies. This article reports prolongation of only VEMP peak latencies (in both cervical and ocular recordings). The youngest sibling had prolongation of VEMP latencies, with ABR peak latencies being normal. The assumption we put forth that CMT4F may affect the vestibular pathway first requires to be tested on a larger sample and by longitudinally studying the individuals with disease condition.

Marker Assisted Gene Pyramiding (MAGP) for bacterial blight and blast resistance into mega rice variety "Tellahamsa".

Bacterial blight (BB) and fungal blast diseases are the major biotic constraints that limit rice productivity. To sustain yield improvement in rice, it is necessary to developed yield potential of the rice varieties by incorporation of biotic stress resistance genes. Tellahamsa is a well-adapted popular high yielding rice variety in Telangana state, India. However, the variety is highly susceptible to BB and blast. In this study, simultaneous stepwise transfer of genes through marker-assisted backcross breeding (MABB) strategy was used to introgress two major BB (Xa21 and xa13) and two major blast resistance genes (Pi54 and Pi1) into Tellahamsa. In each generation (from F1 to ICF3) foreground selection was done using gene-specific markers viz., pTA248 (Xa21), xa13prom (xa13), Pi54MAS (Pi54) and RM224 (Pi1). Two independent BC2F1 lines of Tellahamsa/ISM (Cross-I) and Tellahamsa/NLR145 (Cross-II) possessing 92% and 94% recurrent parent genome (RPG) respectively were intercrossed to develop ICF1-ICF3 generations. These gene pyramided lines were evaluated for key agro-morphological traits, quality, and resistance against blast at three different hotspot locations as well as BB at two locations. Two ICF3 gene pyramided lines viz., TH-625-159 and TH-625-491 possessing four genes exhibited a high level of resistance to BB and blast. In the future, these improved Tellahamsa lines could be developed as mega varieties for different agro-climatic zones and also as potential donors for different pre-breeding rice research.

Construction of genotyping-by-sequencing based high-density genetic maps and QTL mapping for fusarium wilt resistance in pigeonpea.

Fusarium wilt (FW) is one of the most important biotic stresses causing yield losses in pigeonpea. Genetic improvement of pigeonpea through genomics-assisted breeding (GAB) is an economically feasible option for the development of high yielding FW resistant genotypes. In this context, two recombinant inbred lines (RILs) (ICPB 2049 × ICPL 99050 designated as PRIL_A and ICPL 20096 × ICPL 332 designated as PRIL_B) and one F2 (ICPL 85063 × ICPL 87119) populations were used for the development of high density genetic maps. Genotyping-by-sequencing (GBS) approach was used to identify and genotype SNPs in three mapping populations. As a result, three high density genetic maps with 964, 1101 and 557 SNPs with an average marker distance of 1.16, 0.84 and 2.60 cM were developed in PRIL_A, PRIL_B and F2, respectively. Based on the multi-location and multi-year phenotypic data of FW resistance a total of 14 quantitative trait loci (QTLs) including six major QTLs explaining >10% phenotypic variance explained (PVE) were identified. Comparative analysis across the populations has revealed three important QTLs (qFW11.1, qFW11.2 and qFW11.3) with upto 56.45% PVE for FW resistance. This is the first report of QTL mapping for FW resistance in pigeonpea and identified genomic region could be utilized in GAB.

Genotyping-by-sequencing of three mapping populations for identification of candidate genomic regions for resistance to sterility mosaic disease in pigeonpea.

Sterility mosaic disease (SMD) is one of the serious production constraints that may lead to complete yield loss in pigeonpea. Three mapping populations including two recombinant inbred lines and one F2, were used for phenotyping for SMD resistance at two locations in three different years. Genotyping-by-sequencing approach was used for simultaneous identification and genotyping of SNPs on above mentioned populations. In total, 212,464, 89,699 and 64,798 SNPs were identified in ICPL 20096 × ICPL 332 (PRIL_B), ICPL 20097 × ICP 8863 (PRIL_C) and ICP 8863 × ICPL 87119 (F2) respectively. By using high-quality SNPs, genetic maps were developed for PRIL_B (1,101 SNPs; 921.21 cM), PRIL_C (484 SNPs; 798.25 cM) and F2 (996 SNPs; 1,597.30 cM) populations. The average inter marker distance on these maps varied from 0.84 cM to 1.65 cM, which was lowest in all genetic mapping studies in pigeonpea. Composite interval mapping based QTL analysis identified a total of 10 QTLs including three major QTLs across the three populations. The phenotypic variance of the identified QTLs ranged from 3.6 to 34.3%. One candidate genomic region identified on CcLG11 seems to be promising QTL for molecular breeding in developing superior lines with enhanced resistance to SMD.

Race and Sex Differences in the Association between Food Insecurity and Type 2 Diabetes.

OBJECTIVE: To examine whether the relationship between food insecurity (FI) and type 2 diabetes (T2D) varies by race/ethnicity and sex. METHODS: We analyzed data from low-income adults participating in the 2009 and 2011 waves of the California Health Interview Survey (CHIS) (N=22,596). We used logistic regression models to estimate the sex and race-specific associations between FI and T2D. RESULTS: We observed positive associations between low food security and T2D for White men (AOR: 1.9, 95% CI: 1.2, 3.2), and between very low food security and T2D for White women (AOR: 1.6 95% CI: 1.1, 2.5). In Latinas, we observed positive associations between both low food security (AOR: 1.7, 95% CI: 1.3, 2.2) and very low food security (AOR: 1.8, 95% CI: 1.2, 2.6) and T2D. We did not observe any associations between FI and T2D in Latino men, or African American women and men. CONCLUSION: The relationship between FI and T2D may be moderated by race and sex. For African Americans and Latino men, other distal factors may modify the effect of FI on rates of T2D.

Spatially Modelling the Association Between Access to Recreational Facilities and Exercise: The 'Multi-Ethnic Study of Atherosclerosis'.

Numerous studies have investigated the relationship between the built environment and physical activity. However these studies assume that these relationships are invariant over space. In this study, we introduce a novel method to analyze the association between access to recreational facilities and exercise allowing for spatial heterogeneity. In addition, this association is studied before and after controlling for crime, a variable that could explain spatial heterogeneity of associations. We use data from the Chicago site of the Multi-Ethnic Study of Atherosclerosis of 781 adults aged 46 years and over. A spatially varying coefficient Tobit regression model is implemented in the Bayesian setting to allow for the association of interest to vary over space. The relationship is shown to vary over Chicago, being positive in the south but negative or null in the north. Controlling for crime weakens the association in the south with little change observed in northern Chicago. The results of this study indicate that spatial heterogeneity in associations of environmental factors with health may vary over space and deserve further exploration.

Maternal Childhood Adversity, Prepregnancy Obesity, and Gestational Weight Gain.

INTRODUCTION: Growing evidence suggests that exposure to childhood adversity may influence obesity across the life course. High maternal weight complicates pregnancy and increases the risk of child obesity. This study examined the association between maternal childhood adversity and pregnancy-related weight in a large U.S. METHODS: Data on 6,199 pregnancies from 2,873 women followed from 1979 to 2012 by the National Longitudinal Survey of Youth 1979 were analyzed in 2014. Associations between three adversity exposures before age 18 years (history of physical abuse, alcohol problems, or mental illness in the household) and two maternal weight outcomes (prepregnancy obesity and excessive gestational weight gain) were modeled separately using survey-adjusted log-binomial models. RESULTS: After adjusting for race/ethnicity and early-life socioeconomic factors, childhood physical abuse was associated with a 60% increase in the risk of prepregnancy obesity (adjusted risk ratio=1.6, 95% CI=1.1, 2.2). Household alcohol abuse was associated with a 30% increase in prepregnancy obesity (adjusted risk ratio=1.3, 95% CI=1.0, 1.7), as was household mental illness (adjusted risk ratio=1.3, 95% CI=0.8, 1.9), but the mental illness exposure was not significant. Physical abuse and household alcohol abuse were associated with a significant 20% increase in the risk of excessive gestational weight gain; mental illness was not. CONCLUSIONS: Adversity in early life may affect maternal weight before and during pregnancy. Screening and treating women of reproductive age for childhood adversity and its negative effects could significantly reduce obesity-related health outcomes for women and their children.

Methylthioadenosine phosphorylase (MTAP)-deficient T-cell ALL xenografts are sensitive to pralatrexate and 6-thioguanine alone and in combination.

PURPOSE: To investigate the effectiveness of a combination of 6-thioguanine (6-TG) and pralatrexate (PDX) in methylthioadenosine phosphorylase (MTAP)-deficient T-cell acute lymphoblastic leukemia (T-cell ALL). METHODS: CCRF-CEM (MTAP(-/-)) and Molt4 (MTAP(+/+)) T-cell ALL cell lines were treated with 6-TG or PDX and evaluated for efficacy 72 h later. NOD/SCID gamma mice bearing CEM or Molt4 xenografts were treated with 6-TG and PDX alone or in combination to evaluate antitumor effects. RESULTS: CEM cells were more sensitive to 6-TG and PDX in vitro than Molt4. In vivo, CEM cells were very sensitive to PDX and 6-TG, whereas Molt4 cells were highly resistant to 6-TG. A well-tolerated combination of PDX and 6-TG achieved significant tumor regression in CEM xenografts. CONCLUSIONS: The loss of MTAP expression may be therapeutically exploited in T-cell ALL. The combination of 6-TG and PDX, with the inclusion of leucovorin rescue, allows for a safe and effective regimen in MTAP-deficient T-cell ALL.

Genomics-assisted breeding for boosting crop improvement in pigeonpea (Cajanus cajan).

Pigeonpea is an important pulse crop grown predominantly in the tropical and sub-tropical regions of the world. Although pigeonpea growing area has considerably increased, yield has remained stagnant for the last six decades mainly due to the exposure of the crop to various biotic and abiotic constraints. In addition, low level of genetic variability and limited genomic resources have been serious impediments to pigeonpea crop improvement through modern breeding approaches. In recent years, however, due to the availability of next generation sequencing and high-throughput genotyping technologies, the scenario has changed tremendously. The reduced sequencing costs resulting in the decoding of the pigeonpea genome has led to the development of various genomic resources including molecular markers, transcript sequences and comprehensive genetic maps. Mapping of some important traits including resistance to Fusarium wilt and sterility mosaic disease, fertility restoration, determinacy with other agronomically important traits have paved the way for applying genomics-assisted breeding (GAB) through marker assisted selection as well as genomic selection (GS). This would accelerate the development and improvement of both varieties and hybrids in pigeonpea. Particularly for hybrid breeding programme, mitochondrial genomes of cytoplasmic male sterile (CMS) lines, maintainers and hybrids have been sequenced to identify genes responsible for cytoplasmic male sterility. Furthermore, several diagnostic molecular markers have been developed to assess the purity of commercial hybrids. In summary, pigeonpea has become a genomic resources-rich crop and efforts have already been initiated to integrate these resources in pigeonpea breeding.

Leucovorin rescue allows effective high-dose pralatrexate treatment and an increase in therapeutic index in mesothelioma xenografts.

PURPOSE: To investigate the ability of leucovorin (LV) to abrogate dose-limiting toxicities of pralatrexate (PDX) while maintaining efficacy, in vivo. METHODS: H2052 mesothelioma cells were treated with the antifolates methotrexate (MTX), PDX and pemetrexed, with and without LV rescue 24 h later. Cell killing was evaluated 48 h later. Female nude mice bearing H2052 xenografts were treated with varying doses and schedules of the antifolate PDX and LV. RESULTS: In vitro, H2052 cells were more sensitive to PDX as compared to MTX and pemetrexed. Administration of LV 24 h after antifolate treatment reduced efficacy of antifolates MTX and pemetrexed, but not PDX. In vivo, LV was found to reduce toxicity of PDX at the maximum tolerated dose without sacrificing efficacy. Lethal doses of PDX were rescued by LV, and mice bearing the H2052 tumor demonstrated prolonged and enhanced tumor regression. CONCLUSIONS: High-dose PDX with subsequent LV rescue may be a viable treatment strategy in mesothelioma and other cancers. The inclusion of LV rescue into new and existing PDX treatment protocols should be explored as a way to expand the tolerability and effectiveness of PDX in the clinic.

Changes in biologic features between primary and recurrent or relapsed breast cancers.

OBJECTIVE: Changes in ER, PR and Her2 receptor status between primary and metastatic cancer tissue have been suggested in breast cancer. The frequencies of these changes are still not fully understood. The purpose of this study was to evaluate these changes in breast cancer population of Kuwait. SUBJECTS AND METHOD: Changes in the biological features between primary and recurrent disease in 70 patients who presented between 2009 and 2012 was studied. Statistical comparisons between groups was done using chi square test while Kaplan Meier method was used to perform analysis of survival after relapse. All analysis was carried out using the IBM-SPSS statistical software. RESULTS: There was a decrease in ER and PR positivity from 61.4% to 58.6% and 61.4% to 44.3% respectively. The overall change in ER and PR status was 28.5% and 25.7% respectively. There was an increase in the Her2 positivity as the tumor relapsed and overall changes were seen in 5.7% of cases. CONCLUSION: Patients with breast cancer experience change in biological markers through the course of their disease. The changes are more with hormone receptors compared to Her2. Re-biopsy should be considered at relapse if feasible. KEYWORDS: breast cancer, hormone receptors, Her2 neu, receptors, biological features, changes.

Longitudinal associations between neighborhood recreational facilities and change in recreational physical activity in the multi-ethnic study of atherosclerosis, 2000-2007.

Many cross-sectional studies have investigated the relationship between neighborhood physical environment and physical activity. However, few studies have examined this relationship longitudinally, and no study has examined the association between change in objective measurements of physical activity resources and change in physical activity in adults. We used longitudinal data from the Multi-Ethnic Study of Atherosclerosis (2000-2007) of 6,814 adults who were aged 45-84 years at baseline. Physical activity was assessed via a semiquantitative questionnaire at baseline and at 2 follow-up visits (approximately 1.6 and 3.2 years later). We measured the density of recreational facilities within 1 mile of each participant's home address and used linear mixed-effects models to estimate the association between change in recreational facility density and change in physical activity. After adjusting for potential confounders, we found that a greater increase in recreational density was associated with a less pronounced decline in physical activity (mean difference in annual change in physical activity for each 1-unit increase in recreational density over time = 10.3 (95% confidence interval: 0.7, 19.9)). This association was stronger in older adults. Better access to recreational facilities may benefit middle-aged and older adults by enabling them to maintain activity levels as they age.

Development of EST-SSR markers in castor bean (Ricinus communis L.) and their utilization for genetic purity testing of hybrids.

Expressed sequence tag (EST) databases offer opportunity for the rapid development of simple sequence repeat (SSR) markers in crops. Sequence assembly and clustering of 57 895 ESTs of castor bean resulted in the identification of 10 960 unigenes (6459 singletons and 4501 contigs) having 7429 SSRs. On an average, the unigenes contained 1 SSR for every 1.23 kb of unigene sequence. The identified SSRs mostly consisted of dinucleotide (62.4%) and trinucleotide (33.5%) repeats. The AG class was the most common among the dinucleotide motifs (68.9%), whereas the AAG class (25.9%) was predominant among the trinucleotide motifs. A total of 611 primer pairs were designed for the SSRs, having repeat length more than or equal to 20 nucleotides, of which a set of 130 markers were tested and 92 of these yielding robust amplicons were analyzed for their utility in genetic purity assessment of castor bean hybrids. Nine markers were able to detect polymorphism between the parental lines of nine commercial castor bean hybrids (DCH-32, DCH-177, DCH-519, GCH-2, GCH-4, GCH-5, GCH-6, GCH-7, and RHC-1), and their utility in genetic purity testing was demonstrated. These novel EST-SSR markers would be a valuable addition to the growing molecular marker resources that could be used in genetic improvement programmes of castor bean.

Drop-out rates of patients with hepatocellular cancer listed for liver transplantation: outcome with chemoembolization.

Patients with hepatocellular carcinoma (HCC) are assigned model for end stage liver disease (MELD) scores to provide access to liver transplantation (LT). An equitable policy would equate HCC progression beyond acceptable transplantation criteria with death on the waiting list. However, limited information is available regarding this issue. Thus, our aim was to analyze drop-out rates on the waiting list for patients with HCC. Between January 1994 and August 2001, 54 patients with HCC were listed for LT. Patients underwent chemoembolization prior to LT, and were assessed every three months for disease progression until LT. Two patients were stage T1, 45 patients were stage T2, and 7 patients were stage T3 at time of first chemoembolization. Median time was 211 days (range 28-1099 days) for patients that were eventually transplanted. Eight patients were removed from the list. Cumulative probability of drop out on the waiting list, assessed by Kaplan-Meier analysis, was 15% and 25% at 6 and 12 months, respectively. There were no significant differences in age, gender, initial tumor stage, or serum AFP levels in those who eventually underwent LT vs. those who dropped out. In conclusion, neoadjuvant chemoembolization for patients with HCC has a drop-out rate of 15% over 6 months.