Tomato yield heterosis is triggered by a dosage sensitivity of the florigen pathway that fine-tunes shoot architecture

The superiority of hybrids has long been exploited in agriculture, and although many models explaining "heterosis" have been put forth, direct empirical support is limited. Particularly elusive have been cases of heterozygosity for single gene mutations causing heterosis under a genetic model known as overdominance. In tomato (Solanum lycopersicum), plants carrying mutations in SINGLE FLOWER TRUSS (SFT) encoding the flowering hormone florigen are severely delayed in flowering, become extremely large, and produce few flowers and fruits, but when heterozygous, yields are dramatically increased. Curiously, this overdominance is evident only in the background of "determinate" plants, in which the continuous production of side shoots and inflorescences gradually halts due to a defect in the flowering repressor SELF PRUNING (SP). How sp facilitates sft overdominance is unclear, but is thought to relate to the opposing functions these genes have on flowering time and shoot architecture. We show that sft mutant heterozygosity (sft/+) causes weak semi-dominant delays in flowering of both primary and side shoots. Using transcriptome sequencing of shoot meristems, we demonstrate that this delay begins before seedling meristems become reproductive, followed by delays in subsequent side shoot meristems that, in turn, postpone the arrest of shoot and inflorescence production. Reducing SFT levels in sp plants by artificial microRNAs recapitulates the dose-dependent modification of shoot and inflorescence production of sft/+ heterozygotes, confirming that fine-tuning levels of functional SFT transcripts provides a foundation for higher yields. Finally, we show that although flowering delays by florigen mutant heterozygosity are conserved in Arabidopsis, increased yield is not, likely because cyclical flowering is absent. We suggest sft heterozygosity triggers a yield improvement by optimizing plant architecture via its dosage response in the florigen pathway. Exploiting dosage sensitivity of florigen and its family members therefore provides a path to enhance productivity in other crops, but species-specific tuning will be required

Anisotropic Aerogels for Studying Superfluid 3^3He

It may be possible to stabilize new superfluid phases of $^{3}$He with anisotropic silica aerogels. We discuss two methods that introduce anisotropy in the aerogel on length scales relevant to superfluid $^{3}$He. First, anisotropy can be induced with uniaxial strain. A second method generates anisotropy during the growth and drying stages. We have grown cylindrical $\sim$98% aerogels with anisotropy indicated by preferential radial shrinkage after supercritical drying and find that this shrinkage correlates with small angle x-ray scattering (SAXS). The growth-induced anisotropy was found to be $\sim90^\circ$ out of phase relative to that induced by strain. This has implications for the possible stabilization of superfluid phases with specific symmetry.Comment: 6 pages, 4 figures, submitted to Quantum Fluids and Solids (QFS) conference 200

Revisiting Epidermal Growth Factor Receptor (EGFR) Amplification as a Target for Anti-EGFR Therapy: Analysis of Cell-Free Circulating Tumor DNA in Patients With Advanced Malignancies.

PurposeTo date, evidence for tissue epidermal growth factor receptor (EGFR) overexpression as a biomarker for anti-EGFR therapies has been weak. We investigated the genomic landscape of EGFR amplification in blood-derived cell-free tumor DNA (cfDNA) across diverse cancers and the role of anti-EGFR therapies in achieving response.MethodsWe assessed EGFR amplification status among 28,584 patients with malignancies evaluated by clinical-grade next-generation sequencing (NGS) of blood-derived cfDNA (54- to 73-gene panel). Furthermore, we curated the clinical characteristics of 1,434 patients at the University of California San Diego who had cfDNA testing by this NGS test.ResultsOverall, EGFR amplification was detected in cfDNA from 8.5% of patients (2,423 of 28,584), most commonly in colorectal (16.3% [458 of 2,807]), non-small-cell lung (9.0% [1,096 of 12,197]), and genitourinary cancers (8.1% [170 of 2,104]). Most patients had genomic coalterations (96.9% [95 of 98]), frequently involving genes affecting other tyrosine kinases (72.4% [71 of 98]), mitogen-activated protein kinase cascades (56.1% [55 of 98]), cell-cycle-associated signals (52.0% [51 of 98]), and the phosphoinositide 3-kinase pathway (35.7% [35 of 98]). EGFR amplification emerged in serial cfDNA after various anticancer therapies (n = 6), including checkpoint inhibitors (n = 4), suggesting a possible role for these amplifications in acquired resistance. Nine evaluable patients with EGFR amplification were treated with anti-EGFR-based regimens; five (55.6%) achieved partial responses, including three patients whose tissue NGS lacked EGFR amplification.ConclusionEGFR amplification was detected in cfDNA among 8.5% of 28,584 diverse cancers. Most patients had coexisting alterations. Responses were observed in five of nine patients who received EGFR inhibitors. Incorporating EGFR inhibitors into the treatment regimens of patients harboring EGFR amplification in cfDNA merits additional study

The evolution of inflorescence diversity in the nightshades and heterochrony during meristem maturation

One of the most remarkable manifestations of plant evolution is the diversity for floral branching systems. These "inflorescences" arise from stem cell populations in shoot meristems that mature gradually to reproductive states in response to environmental and endogenous signals. The morphology of the shoot meristem maturation process is conserved across distantly related plants, raising the question of how diverse inflorescence architectures arise from seemingly common maturation programs. In tomato and related nightshades (Solanaceae), inflorescences range from solitary flowers to highly branched structures bearing hundreds of flowers. Since reproductive barriers between even closely related Solanaceae have precluded a genetic dissection, we captured and compared meristem maturation transcriptomes from five domesticated and wild species reflecting the evolutionary continuum of inflorescence complexity. We find these divergent species share hundreds of dynamically expressed genes, enriched for transcription factors. Meristem stages are defined by distinct molecular states and point to modified maturation schedules underlying architectural variation. These modified schedules are marked by a peak of transcriptome expression divergence during the reproductive transition, driven by heterochronic shifts of dynamic genes, including transcriptional regulators with known roles in flowering. Thus, evolutionary diversity in Solanaceae inflorescence complexity is determined by subtle modifications of transcriptional programs during a critical transitional window of meristem maturation, which we propose underlies similar cases of plant architectural variation. More broadly, our findings parallel the recently described transcriptome "inverse hourglass" model for animal embryogenesis, suggesting both plant and animal morphological variation is guided by a mid-development period of transcriptome divergence

Magnetoresistance of UPt3

We have performed measurements of the temperature dependence of the magnetoresistance up to 9 T in bulk single crystals of UPt3 with the magnetic field along the b axis, the easy magnetization axis. We have confirmed previous results for transverse magnetoresistance with the current along the c axis, and report measurements of the longitudinal magnetoresistance with the current along the b axis. The presence of a linear term in both cases indicates broken orientational symmetry associated with magnetic order. With the current along the c axis the linear term appears near 5 K, increasing rapidly with decreasing temperature. For current along the b axis the linear contribution is negative.Comment: 6 pages, 3 figures, submitted to Quantum Fluids and Solids Conference (QFS 2006

Positive Surgical Margins in the 10 Most Common Solid Cancers.

A positive surgical margin (PSM) following cancer resection oftentimes necessitates adjuvant treatments and carries significant financial and prognostic implications. We sought to compare PSM rates for the ten most common solid cancers in the United States, and to assess trends over time. Over 10 million patients were identified in the National Cancer Data Base from 1998-2012, and 6.5 million had surgical margin data. PSM rates were compared between two time periods, 1998-2002 and 2008-2012. PSM was positively correlated with tumor category and grade. Ovarian and prostate cancers had the highest PSM prevalence in women and men, respectively. The highest PSM rates for cancers affecting both genders were seen for oral cavity tumors. PSM rates for breast cancer and lung and bronchus cancer in both men and women declined over the study period. PSM increases were seen for bladder, colon and rectum, and kidney and renal pelvis cancers. This large-scale analysis appraises the magnitude of PSM in the United States in order to focus future efforts on improving oncologic surgical care with the goal of optimizing value and improving patient outcomes

Wanted: cancer boss

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62915/1/440978a.pd

The non-coding landscape of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease marked by frequent recurrence and metastasis and stagnant survival rates. To enhance molecular knowledge of HNSCC and define a non-coding RNA (ncRNA) landscape of the disease, we profiled the transcriptome-wide dysregulation of long non-coding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA) using RNA-sequencing data from 422 HNSCC patients in The Cancer Genome Atlas (TCGA). 307 non-coding transcripts differentially expressed in HNSCC were significantly correlated with patient survival, and associated with mutations in TP53, CDKN2A, CASP8, PRDM9, and FBXW7 and copy number variations in chromosomes 3, 5, 7, and 18. We also observed widespread ncRNA correlation to concurrent TP53 and chromosome 3p loss, a compelling predictor of poor prognosis in HNSCCs. Three selected ncRNAs were additionally associated with tumor stage, HPV status, and other clinical characteristics, and modulation of their expression in vitro reveals differential regulation of genes involved in epithelial-mesenchymal transition and apoptotic response. This comprehensive characterization of the HNSCC non-coding transcriptome introduces new layers of understanding for the disease, and nominates a novel panel of transcripts with potential utility as prognostic markers or therapeutic targets