Single- and multiple-trait quantitative trait locus analyses for seed oil and protein contents of soybean populations with advanced breeding line background.

Soybean seed oil and protein contents are negatively correlated, posing challenges to enhance both traits simultaneously. Previous studies have identified numerous oil and protein QTLs via single-trait QTL analysis. Multiple-trait QTL methods were shown to be superior but have not been applied to seed oil and protein contents. Our study aimed to evaluate the effectiveness of single- and multiple-trait multiple interval mapping (ST-MIM and MT-MIM, respectively) for these traits using three recombinant inbred line populations from advanced breeding line crosses tested in four environments. Using original and simulated data, we found that MT-MIM did not outperform ST-MIM for our traits with high heritability (H2 > 0.84). Empirically, MT-MIM confirmed only five out of the seven QTLs detected by ST-MIM, indicating single-trait analysis was sufficient for these traits. All QTLs exerted opposite effects on oil and protein contents with varying protein-to-oil additive effect ratios (-0.4 to -4.8). We calculated the economic impact of the allelic variations via estimated processed values (EPV) using the National Oilseed Processors Association (NOPA) and High Yield + Quality (HY + Q) methods. Oil-increasing alleles had positive effects on both EPVNOPA and EPVHY+Q when the protein-to-oil ratio was low (-0.4 to -0.7). However, when the ratio was high (-4.1 to -4.8), oil-increasing alleles increased EPVNOPA and decreased EPVHY+Q, which penalizes low protein meal. In conclusion, single-trait QTL analysis is adequately effective for high heritability traits like seed oil and protein contents. Additionally, the populations' elite pedigrees and varying protein-to-oil ratios provide potential lines for further yield assessment and direct integration into breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01489-2.

A chromosome 16 deletion conferring a high sucrose phenotype in soybean.

KEY MESSAGE: Sucrose in soybean seeds is desirable for many end-uses. Increased sucrose contents were discovered to associate with a chromosome 16 deletion resulting from fast neutron irradiation. Soybean is one of the most economically important crops in the United States. A primary end-use of soybean is for livestock feed. Therefore, genetic improvement of seed composition is one of the most important goals in soybean breeding programs. Sucrose is desired in animal feed due to its role as an easily digestible energy source. An elite soybean line was irradiated with fast neutrons and the seed from plants were screened for altered seed composition with near-infrared spectroscopy (NIR). One mutant line, G15FN-54, was found to have higher sucrose content (8-9%) than the parental line (5-6%). Comparative genomic hybridization (CGH) revealed three large deletions on chromosomes (Chrs) 10, 13, and 16 in the mutant, which were confirmed through whole genome sequencing (WGS). A bi-parental population derived from the mutant G15FN-54 and the cultivar Benning was developed to conduct a bulked segregant analysis (BSA) with SoySNP50K BeadChips, revealing that the deletion on Chr 16 might be responsible for the altered phenotype. The mapping result using the bi-parental population confirmed that the deletion on Chr 16 conferred elevated sucrose content and a total of 21 genes are located within this Chr 16 deletion. NIR and high-pressure liquid chromatography (HPLC) were used to confirm the stability of the phenotype across generations in the bi-parental population. The mutation will be useful to understand the genetic control of soybean seed sucrose content.

Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma.

OBJECTIVE: To demonstrate that shared antibody responses in endometriosis and endometriosis-associated ovarian cancer spontaneously antagonize malignant progression and can be leveraged to develop future immunotherapies. METHODS: B cells from cyopreserved clear cell ovarian carcinoma (CCC, n = 2), endometrioid ovarian carcinoma (EC, n = 2), and endometriomas (n = 2) were isolated, activated, and EBV-immortalized. Antibodies were purified from B cell supernatants and used for screening arrays containing most of the human proteome. Targets were prioritized based on accessibility (transmembrane or secreted proteins), expression in endometriosis and cancer, and concurrent IgA and IgG responses. We focused on antibodies targeting tumor-promoting syndecan binding protein (SDCBP) to demonstrate anti-tumor activity. Immunoblots and qPCR were performed to assess SDCBP expression in ovarian cancer and endometriosis cell lines and tumor samples. Recombinant IgG4 was generated using the variable heavy and light chains of dominant B cell receptors (BCRs) reacting against the extracellular domain of SDCBP, and used in in vivo studies in human CCC- and high-grade serous ovarian carcinoma (HGSOC)-bearing immunodeficient mice. RESULTS: Nine accessible proteins detected by both IgA and IgG were identified in all samples - including SDCBP, which is expressed in ovarian carcinomas of multiple histologies. Administration of α-SDCBP IgG4 in OVCAR3 (HGSOC), TOV21G and RMG-I (CCC) tumor-bearing mice significantly decreased tumor volume compared to control irrelevant IgG4. CONCLUSIONS: Spontaneous antibody responses exert suboptimal but measurable immune pressure against malignant progression in ovarian carcinomas. Using tumor-derived antibodies for developing novel immunotherapeutics warrants further investigation.

The impact of distance to closest negative margin on survival after pelvic exenteration.

OBJECTIVE: To determine the effect of distance to closest negative margin on survival after pelvic exenteration (PE). METHODS: In this retrospective analysis of PE at Moffitt Cancer Center from 2000 to 2019, baseline characteristics, clinical details, and outcomes were ascertained. Distance to closest negative margin was measured. Close and distant negative margins were defined as <3 mm and ≥3 mm from malignancy to nearest surgical margin, respectively. Overall survival (OS) and progression-free survival (PFS) were determined, and Kaplan-Meier curves were compared. Cox proportional hazards regression was used to examine the association of margin status with OS and PFS. RESULTS: Of 124 PEs with malignancy, 80 (64.5%) had negative margins. Median survival was 62 (95% confidence interval [CI] 27-70) months for negative and 21 (95% CI 15-29) months for positive margins. Of 76 with negative margins and documented margin length, 26 had close and 50 had distant margins. Median survival was 32 (95% CI 14-62) months for close and 111 (95% CI 42-166) months for distant margins. Distant margins were associated with improved OS (p = 0.0054) and PFS (p = 0.0099) compared to close margins. After adjusting for other prognostic factors, patients with distant margins had significantly decreased risk of all-cause mortality (HR 0.39, 95% CI 0.19-0.78; p = 0.008) and progression (HR 0.48, 95% CI 0.23-0.99; p = 0.04) compared to positive margins. No significant differences in OS or PFS were observed between close and positive margins. This survival benefit remained among those with cervical cancer. Median survival in this cohort was 34.1 (95% CI 2.0-69.8) months for close and 165.7 (95% CI 24.5-165.7) for distant margins. CONCLUSIONS: Distant margins following PE are associated with improved OS and PFS compared to close margins.

Trends in ureteral surgery on an academic gynecologic oncology service.

OBJECTIVE: To describe the incidence, complications, and trends associated with ureteral surgeries on a gynecologic oncology service in the context of a fellowship training program over a 24-year period. METHODS: We conducted a retrospective cohort analysis of ureteral surgeries by gynecologic oncologists at either Moffitt Cancer Center or Tampa General Hospital from 1997 to 2020. Patient characteristics, predisposing factors, location and type of injury, repair method, postoperative management and complications were abstracted from the medical record. The recent cohort (2005-2020) was compared to our prior series (1997-2004). RESULTS: Eighty-eight cases were included. The average number of ureteral surgeries per year decreased from 5.75 (1997-2004) to 2.63 (2005-2020). Of 46 iatrogenic injuries, 45 were recognized and repaired intraoperatively. Ureteral transection was the most common type (85% [39 of 46]) and the distal 5 cm was the most common location of injury (63% [29 of 46]). Ureteroneocystostomy was the most common method of repair (83% [73 of 88]). Postoperative management, including stenting and imaging, has not changed significantly. Length of urinary catheter usage decreased in the recent cohort without associated complications. Five patients had major postoperative complications and 4 involved the urinary tract. Of those with follow-up, 96% (66 of 69) of ureteroneocystostomies and 75% (9 of 12) of ureteroureterostomies had radiologically normal urinary tracts. CONCLUSIONS: Ureteral surgery is necessary in the case of injury or involvement with invasive disease. There has been a decrease in number of procedures. Ureteroneocystostomy has remained the most common method of reconstruction for both injury and resection with acceptable postoperative complication rates.

Lagged Relationships Among Chemotherapy-Induced Peripheral Neuropathy, Sleep Quality, and Physical Activity During and After Chemotherapy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is well-documented and can become chronic for up to a third of patients. CIPN management is hampered by limited pharmacological options. Thus, identifying modifiable behaviors that influence CIPN may help inform future interventions. PURPOSE: The purpose of the current study was to examine bidirectional relationships between sleep quality, physical activity, and CIPN during and after chemotherapy. METHODS: Participants were 138 women with gynecologic cancer (M age = 61, 94% white, 96% non-Hispanic), collected as part of an ongoing study. Assessments occurred at postcycle 1, postcycle 6, and 6- and 12-month postchemotherapy. CIPN (EORTC-CIPN20), sleep quality (PSQI), and physical activity (IPAQ) were assessed via self-report. Objective physical activity was assessed via wrist actigraphy. Latent change score models were used to examine lagged relationships between CIPN, sleep quality, and physical activity pairs. RESULTS: Over the study period, sleep quality was found to contribute to CIPN (p = .001), but not the reverse (p > .05). Bidirectional relationships were observed between CIPN and both objective and subjective walking (ps ≤ .001). Illustrations of these relationships showed that patients with less CIPN early in treatment demonstrate more substantial increases in walking over time, while those with higher CIPN demonstrate more consistent levels of walking during and after treatment. CONCLUSIONS: These findings suggest that worse sleep quality and lower walking levels may contribute to the course and maintenance of CIPN. Future investigation should evaluate the impact of early interventions aimed at improving sleep quality and encouraging physical activity in patients treated with chemotherapy.

Mining QTLs for elevated protein and other major seed composition traits from diverse soybean germplasm.

Soybean is the world's largest source of protein for animal feed and the second largest source of vegetable oil. Improving the seed protein of soybean without negatively affecting yield and oil content is an important goal for soybean breeders. A population consisting of 132 recombinant inbred lines (RILs) was developed by crossing an elite breeding line, G00-3213 with a plant introduction, PI 594458A, with elevated protein content. In 2016 and 2017, each of the RILs was grown as a single row in Watkinsville, GA, while in 2018, the population was grown at two locations. The seed composition of RILs was analyzed with near-infrared (NIR) spectroscopy. The RIL population was genotyped using the SoySNP6k BeadChip for quantitative trait locus (QTL) mapping. Significant genotype × environment interaction was observed. QTL analyses in and across four environments identified 16, 10, 10, 16, and 5 QTLs for protein, oil, sucrose, and normalized cysteine and methionine contents, respectively. QTLs for protein content identified on chromosomes (Chrs) 3, 6, 13, and 20 were detected in multiple environments. Eight genomic regions on Chrs 3, 6, 8, 10, 13, 17, and 20 were detected that influenced two to four traits, indicating that pleiotropic or linkage effects of these loci may influence multiple seed composition traits. The results of this research provide additional genomic resources for genetic improvement of seed composition and help breeders to better understand the environmental impacts on these QTLs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01242-z.

Identification of SNP markers associated with soybean fatty acids contents by genome-wide association analyses.

Composition of fatty acids (FAs) in soybean seed is important for the quality and uses of soybean oil. Using gas chromatography, we have measured soybean FAs profiles of 621 soybean accessions (maturity groups I through IV) grown in five different environments; Columbus, OH (2015), Wooster, OH (2014 and 2015), Plymouth, NC (2015), and Urbana, IL (2015). Using publicly available SoySNP50K genotypic data and the FA profiles from this study, a genome-wide association analysis was completed with a compressed mixed linear model to identify 43 genomic regions significantly associated with a fatty acid at a genome wide significance threshold of 5%. Among these regions, one and three novel genomic regions associated with palmitic acid and stearic acid, respectively, were identified across all five environments. Additionally, nine novel environment-specific FA-related genomic regions were discovered providing new insights into the genetics of soybean FAs. Previously reported FA-related loci, such as FATB1a, SACPD-C, and KASIII, were also confirmed in this study. Our results will be useful for future functional studies and marker-assisted breeding for soybean FAs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01216-1.

MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques (Macaca mulatta) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoroacetate ([18F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [18F]fluorothymidine ([18F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1-rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans.

Tuning the Redox Activity of Metal-Organic Frameworks for Enhanced, Selective O2 Binding: Design Rules and Ambient Temperature O2 Chemisorption in a Cobalt-Triazolate Framework.

Metal-organic frameworks (MOFs) with coordinatively unsaturated metal sites are appealing as adsorbent materials due to their tunable functionality and ability to selectively bind small molecules. Through the use of computational screening methods based on periodic density functional theory, we investigate O2 and N2 adsorption at the coordinatively unsaturated metal sites of several MOF families. A variety of design handles are identified that can be used to modify the redox activity of the metal centers, including changing the functionalization of the linkers (replacing oxido donors with sulfido donors), anion exchange of bridging ligands (considering µ-Br-, µ-Cl-, µ-F-, µ-SH-, or µ-OH- groups), and altering the formal oxidation state of the metal. As a result, we show that it is possible to tune the O2 affinity at the open metal sites of MOFs for applications involving the strong and/or selective binding of O2. In contrast with O2 adsorption, N2 adsorption at open metal sites is predicted to be relatively weak across the MOF dataset, with the exception of MOFs containing synthetically elusive V2+ open metal sites. As one example from the screening study, we predicted that exchanging the µ-Cl- ligands of M2Cl2(BBTA) (H2BBTA = 1H,5H-benzo(1,2-d:4,5-d')bistriazole) with µ-OH- groups would significantly enhance the strength of O2 adsorption at the open metal sites without a corresponding increase in the N2 affinity. Experimental investigation of Co2Cl2(BBTA) and Co2(OH)2(BBTA) confirms that the former exhibits weak physisorption of both N2 and O2, whereas the latter is capable of chemisorbing O2 at room temperature in a highly selective manner. The O2 chemisorption behavior is attributed to the greater electron-donating character of the µ-OH- ligands and the presence of H-bonding interactions between the µ-OH- bridging ligands and the reduced O2 adsorbate.

CD4+CD25+ T Cells are Essential for Behavioral Effects of Lactobacillus rhamnosus JB-1 in Male BALB/c mice.

Over the past decade there has been increasing interest in the involvement of the microbiota-gut-brain axis in mental health. However, there are major gaps in our knowledge regarding the complex signaling systems through which gut microbes modulate the CNS. The immune system is a recognized mediator in the bidirectional communication continuously occurring between gut and brain. We previously demonstrated that Lactobacillus rhamnosus JB-1 (JB-1), a bacterial strain that has anxiolytic- and antidepressant-like effects in mice, modulates the immune system through induction of immunosuppressive T regulatory cells. Here we examined a potential causal relationship between JB-1 induced regulatory T cells and the observed effects on behaviour. We found that depletion of regulatory T cells, via treatment with monoclonal antibody against CD25, inhibited the antidepressant- and anxiolytic-like effects induced by 4-week oral administration of JB-1 in mice. Ly6Chi monocytes were found to be decreased in JB-1 fed mice with intact regulatory T cells, but not in JB-1 fed mice following depletion. Furthermore, adoptive transfer of CD4+CD25+ cells, from JB-1 treated donor mice, but not from controls, induced antidepressant- and anxiolytic-like effects in recipient mice. Ly6Chi monocytes were also significantly decreased in mice receiving CD4+CD25+ cells from JB1 fed donors. This study identifies cells within the CD4+CD25+ population, most likely regulatory T cells, as both necessary and sufficient in JB-1-induced antidepressant- and anxiolytic-like effects in mice, providing novel mechanistic insight into microbiota-gut-brain communication in addition to highlighting the potential for immunotherapy in psychiatric disorders.

Prenatal low-dose penicillin results in long-term sex-specific changes to murine behaviour, immune regulation, and gut microbiota.

Growing evidence suggests that environmental disruptors of maternal microbes may have significant detrimental consequences for the developing fetus. Antibiotic exposure during early life can have long-term effects on neurodevelopment in mice and humans. Here we explore whether exposure to low-dose penicillin during only the last week of gestation in mice has long-term effects on offspring behaviour, brain, immune function, and gut microbiota. We found that this treatment had sex-specific effects in the adult mouse offspring. Female, but not male, mice demonstrated decreased anxiety-like behaviours, while male, but not female, mice had abnormal social behaviours which correlated with altered brain expression of AVPR1A, AVPR1B, and OXTR, and decreases in the balance of splenic FOXP3+ regulatory T cells. Prenatal penicillin exposure also led to distinct microbiota compositions that clustered differently by sex. These data suggest that exposure of pregnant mice to even a low dose of penicillin through only the last week before birth is nonetheless sufficient to induce long-term sex-specific developmental changes in both male and female offspring.

High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity.

INTRODUCTION: To evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer. METHODS: In this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test. RESULTS: Twenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3-52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2-44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3-4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3-4 toxicity. CONCLUSION: High-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity.

Workflow for the Quantification of Soluble and Insoluble Carbohydrates in Soybean Seed.

Soybean seed composition has a profound impact on its market value and commercial use as an important commodity. Increases in oil and protein content have been historically pursued by breeders and genetic engineers; consequently, rapid methods for their quantification are well established. The interest in complete carbohydrate profiles in mature seeds, on the other hand, has recently increased due to numerous attempts to redirect carbohydrates into oil and protein or to offer specialty seed with a specific sugar profile to meet animal nutritional requirements. In this work, a sequential protocol for quantifying reserve and structural carbohydrates in soybean seed was developed and validated. Through this procedure, the concentrations of soluble sugars, sugar alcohols, starch, hemicellulose, and crystalline cellulose can be determined in successive steps from the same starting material using colorimetric assays, LC-MS/MS, and GC-MS. The entire workflow was evaluated using internal standards to estimate the recovery efficiency. Finally, it was successfully applied to eight soybean genotypes harvested from two locations, and the resulting correlations of carbohydrate and oil or protein are presented. This methodology has the potential not only to guide soybean cultivar optimization processes but also to be expanded to other crops with only slight modifications.

Genome-wide association study of seed protein, oil and amino acid contents in soybean from maturity groups I to IV.

KEY MESSAGE: Genomic regions associated with seed protein, oil and amino acid contents were identified by genome-wide association analyses. Geographic distributions of haplotypes indicate scope of improvement of these traits. Soybean [Glycine max (L.) Merr.] protein and oil are used worldwide in feed, food and industrial materials. Increasing seed protein and oil contents is important; however, protein content is generally negatively correlated with oil content. We conducted a genome-wide association study using phenotypic data collected from five environments for 621 accessions in maturity groups I-IV and 34,014 markers to identify quantitative trait loci (QTL) for seed content of protein, oil and several essential amino acids. Three and five genomic regions were associated with seed protein and oil contents, respectively. One, three, one and four genomic regions were associated with cysteine, methionine, lysine and threonine content (g kg-1 crude protein), respectively. As previously shown, QTL on chromosomes 15 and 20 were associated with seed protein and oil contents, with both exhibiting opposite effects on the two traits, and the chromosome 20 QTL having the most significant effect. A multi-trait mixed model identified trait-specific QTL. A QTL on chromosome 5 increased oil with no effect on protein content, and a QTL on chromosome 10 increased protein content with little effect on oil content. The chromosome 10 QTL co-localized with maturity gene E2/GmGIa. Identification of trait-specific QTL indicates feasibility to reduce the negative correlation between protein and oil contents. Haplotype blocks were defined at the QTL identified on chromosomes 5, 10, 15 and 20. Frequencies of positive effect haplotypes varied across maturity groups and geographic regions, providing guidance on which alleles have potential to contribute to soybean improvement for specific regions.

Identification and characterization of a fast-neutron-induced mutant with elevated seed protein content in soybean.

KEY MESSAGE: Protein content of soybean is critical for utility of soybean meal. A fast-neutron-induced deletion on chromosome 12 was found to be associated with increased protein content. Soybean seed composition affects the utility of soybean, and improving seed composition is an essential breeding goal. Fast neutron radiation introduces genomic mutations resulting in novel variation for traits of interest. Two elite soybean lines were irradiated with fast neutrons and screened for altered seed composition. Twenty-three lines with altered protein, oil, or sucrose content were selected based on near-infrared spectroscopy data from five environments and yield tested at five locations. Mutants with significantly increased protein averaged 19.1-36.8 g kg-1 more protein than the parents across 10 environments. Comparative genomic hybridization (CGH) identified putative mutations in a mutant, G15FN-12, that has 36.8 g kg-1 higher protein than the parent genotype, and whole genome sequencing (WGS) of the mutant has confirmed these mutations. An F2:3 population was developed from G15FN-12 to determine association between genomic changes and increased protein content. Bulked segregant analysis of the population using the SoySNP50K BeadChip identified a CGH- and WGS-confirmed deletion on chromosome 12 to be responsible for elevated protein content. The population was genotyped using a KASP marker designed at the mutation region, and significant association (P < 0.0001) between the deletion on chromosome 12 and elevated protein content was observed and confirmed in the F3:4 generation. The F2 segregants homozygous for the deletion averaged 27 g kg-1 higher seed protein and 8 g kg-1 lower oil than homozygous wild-type segregants. Mutants with altered seed composition are a new resource for gene function studies and provide elite materials for genetic improvement of seed composition.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Smallest Optical Gap for Pt(II)-Pt(IV) Mixed-Valence Pt-Cl and Pt-Br Chain Complexes Achieved by Using a Multiple-Hydrogen-Bond Approach.

A multiple-hydrogen-bond approach was applied to shorten Pt-X-Pt distances in Cl- and Br-bridged Pt chain complexes. [Pt(dabdOH)2Cl]Cl2 (5) and [Pt(dabdOH)2Br]Br2 (6) (dabdOH = (2 S,3 S)-2,3-diaminobutane-1,4-diol) contain hydroxy groups, which form additional hydrogen bonds with counteranions. 5 has the shortest Pt-Cl-Pt distance (5.0747(8) Å) of all Cl-bridged Pt chain complexes reported to date. Furthermore, the smallest optical gap (1.45 eV for 5 and 1.19 eV for 6) in any Cl- or Br-bridged Pt chain complex was achieved. 6 has the highest electrical conductivity (1.9 × 10-5 S cm-1 at room temperature) of all Br-bridged Pt chain complexes. This study shows that the introduction of additional hydrogen bonds between the ligands and halides is effective to enhance the electronic properties of halogen-bridged metal complexes.

Using simple radiologic measurements to anticipate surgical challenge in endometrial cancer: a prospective study.

OBJECTIVES: To determine if linear measurements of adiposity from pre-operative imaging can improve anticipation of surgical difficulty among endometrial cancer patients. METHODS: Eighty patients with newly diagnosed endometrial cancer were enrolled. Routine pre-operative imaging (MRI or CT) was performed. Radiologic linear measurements of the following were obtained: anterior-to-posterior skin distance; anterior skin to anterior edge of L5 distance (total anterior); anterior peritoneum to anterior edge of L5 distance (visceral obesity); and posterior edge of L5 to posterior skin distance (total posterior). Surgeons completed questionnaires quantifying preoperative anticipated operative difficulty and postoperative reported operative difficulty. The primary objective was to assess for a correlation between linear measurements of visceral fat and reported operative difficulty. RESULTS: Seventy-nine patients had questionnaires completed, preoperative imaging obtained, and surgery performed. Univariate analysis showed all four linear measurements, body mass index, weight, and anticipated operative difficulty were associated with increased reported operative difficulty (P< 0.05). Multivariate analysis demonstrated that body mass index and linear measurements visceral obesity and total posterior were independently associated with increased reported operative difficulty (P< 0.05). Compared with body mass index, the visceral obesity measurement was more sensitive and specific for predicting increased reported operative difficulty (visceral obesity; sensitivity 54%, specificity 91 %; body mass index; sensitivity 38%, specificity 89%). A difficulty risk model combining body mass index, visceral obesity, and total posterior demonstrated better predictive performance than any individual preoperative variable. CONCLUSIONS: Simple linear measurements of visceral fat obtained from preoperative imaging are more predictive than body mass index alone in anticipating surgeon-reported operative difficulty. These easily obtained measurements may assist in preoperative decision making in this challenging patient population.

Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer.

Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC.