Harnessing translational research in wheat for climate resilience.

Despite being the world's most widely grown crop, research investments in wheat (Triticum aestivum and Triticum durum) fall behind those in other staple crops. Current yield gains will not meet 2050 needs, and climate stresses compound this challenge. However, there is good evidence that heat and drought resilience can be boosted through translating promising ideas into novel breeding technologies using powerful new tools in genetics and remote sensing, for example. Such technologies can also be applied to identify climate resilience traits from among the vast and largely untapped reserve of wheat genetic resources in collections worldwide. This review describes multi-pronged research opportunities at the focus of the Heat and Drought Wheat Improvement Consortium (coordinated by CIMMYT), which together create a pipeline to boost heat and drought resilience, specifically: improving crop design targets using big data approaches; developing phenomic tools for field-based screening and research; applying genomic technologies to elucidate the bases of climate resilience traits; and applying these outputs in developing next-generation breeding methods. The global impact of these outputs will be validated through the International Wheat Improvement Network, a global germplasm development and testing system that contributes key productivity traits to approximately half of the global wheat-growing area.

Detection and characterization of fungus (Magnaporthe oryzae pathotype Triticum) causing wheat blast disease on rain-fed grown wheat (Triticum aestivum L.) in Zambia.

Wheat blast caused by Magnaporthe oryzae pathotype Triticum (MoT) is a threat to wheat production especially in the warmer-humid environments. In Zambia, wheat blast symptoms were observed for the first time on wheat (Triticum aestivum L.) grown in experimental plots and five farmers' fields in Mpika district of Muchinga Province during the 2017-18 rainy season. Infected plants showed the typical wheat blast symptoms with the spike becoming partially or completely bleached with the blackening of the rachis in a short span of time. Incidence of blast symptoms on nearly all wheat heads was high and ranged from 50 to 100%. Examination of diseased plant leaves showed the presence of elliptical, grayish to tan necrotic lesions with dark borders on the leaf often mixed with other foliar diseases. A study was conducted to isolate and identify the causal pathogen(s) using classical and molecular methods and determine the pathogenicity of the detected disease causal agent. Morphobiometrical determination of causal pathogen revealed conidia with characteristic pear shaped 2-septate hyaline spores associated with M. oryzae species. Preliminary polymerase chain reaction screening of six isolates obtained from wheat blast infected samples with diagnostic primers (MoT3F/R) was conducted at ZARI, Zambia, and subsequent analysis of two isolates with MoT3F/R and C17F/R was performed at USDA-ARS, USA. Both experiments confirmed that MoT is the causal agent of wheat blast in Zambia. Further, pathogenicity tests performed with pure culture isolates from samples WS4 and WS5 produced typical blast symptoms on all the six inoculated wheat genotypes. Results of this study indicate that MoT is causing wheat blast in rain-fed wheat grown in Zambia, thus making it the first report of MoT in Zambia and Africa. This inter-continental movement of the pathogen (disease) has serious implication for wheat production and trade that needs to be urgently addressed.

Perspective: Whole and Refined Grains and Health-Evidence Supporting "Make Half Your Grains Whole".

Research-based dietary guidelines suggest that consumers "make half their grains whole." Yet some advocate ingesting only whole-grain foods (WGFs) and avoiding all refined-grain foods (RGFs). Some even recommend avoiding all grain-based foods (GBFs). This article will provide arguments to counter negative deductions about GBFs and RGFs, especially staple ones, and to support dietary guidance recommending a balance of GBFs-achieved through the right mix, type, and quantity of WGFs and RGFs. Studies looking at early mortality, body weight, and glucose tolerance and diabetes will be used as examples to characterize the literature about GBFs. The following issues are highlighted: 1) inconsistent findings between epidemiological and interventional studies and impacts of GBFs on health outcomes, and the underreporting of findings showing RGFs neither raise nor lower health risks; 2) multiple confounding and potential interactions make adequate statistical adjustment difficult; 3) nonuniform WGF definitions among studies make comparison of results challenging, especially because some WGFs may contain 49-74% refined grain (RG); 4) binary categorization of GBFs creates bias because nearly all categories of WGFs are recommended, but nearly half the RGF categories are not; 5) ingestion of >5 (30-g) servings RGFs/d and <1 serving WFGs/d creates dietary imbalance; 6) pattern names (e.g., "white bread") may impugn RGFs, when names such as "unbalanced" or "few fruits and vegetables" may more fairly characterize the dietary imbalance; 7) avoidance of all enriched RGs may not only impair status of folate and other B vitamins and certain minerals such as iron and zinc but also decrease acceptability of WGFs; 8) extrapolation beyond median documented intakes in high-WGF consumers (∼48 g whole grain/d) in most cohorts is speculative; 9) recommended dietary patterns such as the Mediterranean diet demonstrate that the right mix of WGFs and RGFs contributes to positive health outcomes.

Correction to: Strategic crossing of biomass and harvest index-source and sink-achieves genetic gains in wheat.

[This corrects the article DOI: 10.1007/s10681-017-2040-z.].

Genetic Yield Gains In CIMMYT's International Elite Spring Wheat Yield Trials By Modeling The Genotype × Environment Interaction.

We calculated the annual genetic gains for grain yield (GY) of wheat (Triticum aestivum L.) achieved over 8 yr of international Elite Spring Wheat Yield Trials (ESWYT), from 2006-2007 (27th ESWYT) to 2014-2015 (34th ESWYT). In total, 426 locations were classified within three main megaenvironments (MEs): ME1 (optimally irrigated environments), ME4 (drought-stressed environments), and ME5 (heat-stressed environments). By fitting a factor analytical structure for modeling the genotype × environment (G × E) interaction, we measured GY gains relative to the widely grown cultivar Attila (GYA) and to the local checks (GYLC). Genetic gains for GYA and GYLC across locations were 1.67 and 0.53% (90.1 and 28.7 kg ha-1 yr-1), respectively. In ME1, genetic gains were 1.63 and 0.72% (102.7 and 46.65 kg ha-1 yr-1) for GYA and GYLC, respectively. In ME4, genetic gains were 2.7 and 0.41% (88 and 15.45 kg ha-1 yr-1) for GYA and GYLC, respectively. In ME5, genetic gains were 0.31 and 1.0% (11.28 and 36.6 kg ha-1 yr-1) for GYA and GYLC, respectively. The high GYA in ME1 and ME4 can be partially attributed to yellow rust races that affect Attila. When G × E interactions were not modeled, genetic gains were lower. Analyses showed that CIMMYT's location at Ciudad Obregon, Mexico, is highly correlated with locations in other countries in ME1. Lines that were top performers in more than one ME and more than one country were identified. CIMMYT's breeding program continues to deliver improved and widely adapted germplasm for target environments.

Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group.

BACKGROUND: The optimum duration of first-line treatment with chemotherapy in combination with bevacizumab in patients with metastatic colorectal cancer is unknown. The CAIRO3 study was designed to determine the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation. METHODS: In this open-label, phase 3, randomised controlled trial, we recruited patients in 64 hospitals in the Netherlands. We included patients older than 18 years with previously untreated metastatic colorectal cancer, with stable disease or better after induction treatment with six 3-weekly cycles of capecitabine, oxaliplatin, and bevacizumab (CAPOX-B), WHO performance status of 0 or 1, and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) to either maintenance treatment with capecitabine and bevacizumab (maintenance group) or observation (observation group). Randomisation was done centrally by minimisation, with stratification according to previous adjuvant chemotherapy, response to induction treatment, WHO performance status, serum lactate dehydrogenase concentration, and treatment centre. Both patients and investigators were aware of treatment assignment. We assessed disease status every 9 weeks. On first progression (defined as PFS1), patients in both groups were to receive the induction regimen of CAPOX-B until second progression (PFS2), which was the study's primary endpoint. All endpoints were calculated from the time of randomisation. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00442637. FINDINGS: Between May 30, 2007, and Oct 15, 2012, we randomly assigned 558 patients to either the maintenance group (n=279) or the observation group (n=279). Median follow-up was 48 months (IQR 36-57). The primary endpoint of median PFS2 was significantly improved in patients on maintenance treatment, and was 8·5 months in the observation group and 11·7 months in the maintenance group (HR 0·67, 95% CI 0·56-0·81, p<0·0001). This difference remained significant when any treatment after PFS1 was considered. Maintenance treatment was well tolerated, although the incidence of hand-foot syndrome was increased (64 [23%] patients with hand-foot skin reaction during maintenance). The global quality of life did not deteriorate during maintenance treatment and was clinically not different between treatment groups. INTERPRETATION: Maintenance treatment with capecitabine plus bevacizumab after six cycles of CAPOX-B in patients with metastatic colorectal cancer is effective and does not compromise quality of life. FUNDING: Dutch Colorectal Cancer Group (DCCG). The DCCG received financial support for the study from the Commissie Klinische Studies (CKS) of the Dutch Cancer Foundation (KWF), Roche, and Sanofi-Aventis.

Randomized phase II study comparing efficacy and safety of combination-therapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel alone at progression as first-line chemotherapy in patients with HER2+ metastatic breast cancer: HERTAX trial.

BACKGROUND: Because chemotherapy for metastatic breast cancer (MBC) is associated with relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease progression might be an attractive approach. METHODS: In a multicenter phase II trial, 101 patients with overexpression of human epidermal growth factor receptor 2 (HER2(+)) MBC were randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel alone (H→D) as first-line chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS) after completed sequential or combination therapy. RESULTS: For the H+D group the median PFS was 9.4 vs. 9.9 months for the H→D group and 1-year PFS rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79% vs. 53%, respectively (P = .016), and overall survival was 30.5 vs. 19.7 months, respectively (P = .11). In the H→D group, response rates to monotherapy trastuzumab and subsequent docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of patients in the H+D group and 37% in the H→D group) showed a correlation with longer overall survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively). CONCLUSION: First-line treatment in patients with MBC with H→D resulted in a similar PFS compared with H+D, but the response rate was lower and the overall survival nonsignificantly shorter.

Genetic variation within and between winter wheat genotypes from Turkey, Kazakhstan, and Europe as determined by nucleotide-binding-site profiling.

The genetic diversity within wheat breeding programs across Turkey and Kazakhstan was compared with a selection of European cultivars that represented the genetic diversity across eight European countries and six decades of wheat breeding. To focus the measure of genetic diversity on that relevant to disease-resistant phenotypes, nucleotide-binding-site (NBS) profiling was used to detect polymorphisms associated with the NBS motifs found within the NBS--leucine-rich repeat (LRR) class of resistance (R) genes. Cereal-specific NBS primers, designed specifically to the conserved NBS motifs found within cereal R-genes, provided distinct NBS profiles. Although the genetic diversity associated with NBS motifs was only slightly higher within the Eastern wheat genotypes, the NBS profiles produced by Eastern and European wheat lines differed considerably. Structure analysis divided the wheat genotypes into four groups, which compared well with the origin of the wheat genotypes. The highest levels of genetic diversity were seen for the wheat genotypes from the Genetic Resource Collection held in Ankara, Turkey, as wheat genotypes within breeding programs were genetically more similar. The wheat genotypes from Kazakhstan were the most similar to the European cultivars, reflecting the significant number of eastern European cultivars used in the breeding program in Kazakhstan. In general, the NBS profiles suggested that NBS-LRR R-gene usage in winter wheat breeding in Turkey and Kazakhstan differed from that deployed in European cultivars.

Phase II to III study comparing doxorubicin and docetaxel with fluorouracil, doxorubicin, and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: results of a Dutch Community Setting Trial for the Clinical Trial Group of the Comprehensive Cancer Centre.

PURPOSE: To compare the efficacy and safety of doxorubicin and docetaxel (AT) with fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line chemotherapy for metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients (n = 216) were randomly assigned to either AT (doxorubicin 50 mg/m(2) and docetaxel 75 mg/m2) or FAC (fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2); both regimens were administered on day 1, every 3 weeks. RESULTS: A median number of six cycles was delivered in both arms, with a median relative dose-intensity of more than 98%. Median time to progression (TTP) and median overall survival (OS) were significantly longer for patients on AT compared with FAC (TTP: 8.0 v 6.6 months, respectively; P = .004; and OS: 22.6 v 16.2 months, respectively; P = .019). The overall response rate (ORR) was significantly higher in patients on AT compared with FAC (58% v 37%, respectively; P = .003). The ORR on AT was also higher in patients with visceral disease compared with FAC patients with visceral disease (59% v 36%, respectively; P = .003). There were no differences in grade 3 to 4 neutropenia and infections (AT 89% v FAC 84% and AT 12% v FAC 9%, respectively). Neutropenic fever was more common in AT-treated patients than FAC-treated patients (33% v 9%, respectively; P < .001). Grade 3 to 4 nonhematologic toxicity was infrequent in both arms. Congestive heart failure was observed in 3% and 6% of patients on AT and FAC, respectively. CONCLUSION: In this phase II to III study, AT resulted in a significantly longer TTP and OS and a higher objective ORR than FAC. First-line AT is a valid treatment option for patients with MBC.