Genotyping-by-sequencing-based identification of Arabidopsis pattern recognition receptor RLP32 recognizing proteobacterial translation initiation factor IF1

Activation of plant pattern-triggered immunity (PTI) relies on the recognition of microbe-derived structures, termed patterns, through plant-encoded surface-resident pattern recognition receptors (PRRs). We show that proteobacterial translation initiation factor 1 (IF1) triggers PTI in Arabidopsis thaliana and related Brassicaceae species. Unlike for most other immunogenic patterns, IF1 elicitor activity cannot be assigned to a small peptide epitope, suggesting that tertiary fold features are required for IF1 receptor activation. We have deployed natural variation in IF1 sensitivity to identify Arabidopsis leucine-rich repeat (LRR) receptor-like protein 32 (RLP32) as IF1 receptor using a restriction site-associated DNA sequencing approach. RLP32 confers IF1 sensitivity to rlp32 mutants, IF1-insensitive Arabidopsis accessions and IF1-insensitive Nicotiana benthamiana, binds IF1 specifically and forms complexes with LRR receptor kinases SOBIR1 and BAK1 to mediate signaling. Similar to other PRRs, RLP32 confers resistance to Pseudomonas syringae, highlighting an unexpectedly complex array of bacterial pattern sensors within a single plant species

Limitations of Conventional Contrast-enhanced MRI in Selecting Sentinel Node Biopsy Candidates among DCIS Patients

Purpose: A better predictive model for occult invasive disease in ductal carcinoma in situ (DCIS) patients is essential to guide the tailored use of sentinel node biopsies. We hypothesized that recent improvement of contrast-enhanced breast magnetic resonance imaging (MRI) could provide more accurate information on the presence of occult invasion in DCIS patients. Methods: From a prospectively maintained database, we identified 143 DCIS patients diagnosed with needle biopsies in whom MRI images were available. Results: Sixty-five patients (45.5%) were upstaged to invasive carcinoma after curative surgery. Ultrasonographic lesion size, mass-appearance on mammography, type of needle used, and the presence of suspicious microinvasive foci were associated with increased likelihood of upstaging. Among the features of MRI, only mass-appearance was significantly associated with the presence of invasive disease (p=0.002). However, up to 50% of masses in MRI cases had mass-appearance on mammography as well. Other morphologic and pharmacokinetic features of MRI, such as shape, margin, and patterns of enhancement and washout, did not have a significant association. Conclusion: Among various morphologic and pharmacokinetic parameters of contrast-enhanced MRI, only mass-appearance was associated with occult invasive disease. Our results show the limitations of current contrast-enhanced MRI in predicting invasive disease in patients with preoperative diagnoses of DCIS.Moon HG, 2009, ANN ONCOL, V20, P636, DOI 10.1093/annonc/mdn683Kuerer HM, 2009, J CLIN ONCOL, V27, P279, DOI 10.1200/JCO.2008.18.3103HU M, 2009, P NATL ACAD SCI USA, V106, P3372Gadre SA, 2008, HISTOPATHOLOGY, V53, P545, DOI 10.1111/j.1365-2559.2008.03152.xOkumura Y, 2008, BMC CANCER, V8, DOI 10.1186/1471-2407-8-287Sakorafas GH, 2008, CANCER TREAT REV, V34, P483, DOI 10.1016/j.ctrv.2008.03.001Morrow M, 2008, ANN SURG ONCOL, V15, P2641, DOI 10.1245/s10434-008-0083-zPorembka MR, 2008, ANN SURG ONCOL, V15, P2709, DOI 10.1245/s10434-008-9947-5Lee JW, 2008, J SURG ONCOL, V98, P15, DOI 10.1002/jso.21077Hu M, 2008, CANCER CELL, V13, P394, DOI 10.1016/j.ccr.2008.03.007Ansari B, 2008, BRIT J SURG, V95, P547, DOI 10.1002/bjs.6162Orel S, 2008, J CLIN ONCOL, V26, P703, DOI 10.1200/JCO.2007.14.3594Facius M, 2007, CLIN IMAG, V31, P394, DOI 10.1016/j.clinimag.2007.04.030Kuhl CK, 2007, LANCET, V370, P485Jung EJ, 2007, INT J CANCER, V120, P2331, DOI 10.1002/ijc.22434Nielsen BS, 2007, INT J CANCER, V120, P2086, DOI 10.1002/ijc.22340van der Velden APS, 2006, AM J SURG, V192, P172, DOI 10.1016/j.amjsurg.2006.02.026Goyal A, 2006, BREAST CANCER RES TR, V98, P311, DOI 10.1007/s10549-006-9167-2Mansel RE, 2006, J NATL CANCER I, V98, P599, DOI 10.1093/jnci/djj158Lyman GH, 2005, J CLIN ONCOL, V23, P7703, DOI 10.1200/JCO.2005.08.001Wilkie C, 2005, AM J SURG, V190, P563, DOI 10.1016/j.amjsurg.2005.06.011Groves AM, 2005, MAGN RESON IMAGING, V23, P733, DOI 10.1016/j.mri.2005.06.003Hylton N, 2005, J CLIN ONCOL, V23, P1678, DOI 10.1200/JCO.2005.12.002Leonard GD, 2004, J NATL CANCER I, V96, P906, DOI 10.1093/jnci/djh164Hata T, 2004, J AM COLL SURGEONS, V198, P190, DOI 10.1016/j.jamcollsurg.2003.10.008Hwang EW, 2003, ANN SURG ONCOL, V10, P381, DOI 10.1245/ASO.2003.03.085*AM COLL RAD, 2003, ACR BI RADS BREAST IMorrow M, 2002, CA-CANCER J CLIN, V52, P277Jackman RJ, 2001, RADIOLOGY, V218, P497Brown LF, 1999, CLIN CANCER RES, V5, P1041

What is quantitative plant biology?

Quantitative plant biology is an interdisciplinary field that builds on a long history of biomathematics and biophysics. Today, thanks to high spatiotemporal resolution tools and computational modelling, it sets a new standard in plant science. Acquired data, whether molecular, geometric or mechanical, are quantified, statistically assessed and integrated at multiple scales and across fields. They feed testable predictions that, in turn, guide further experimental tests. Quantitative features such as variability, noise, robustness, delays or feedback loops are included to account for the inner dynamics of plants and their interactions with the environment. Here, we present the main features of this ongoing revolution, through new questions around signalling networks, tissue topology, shape plasticity, biomechanics, bioenergetics, ecology and engineering. In the end, quantitative plant biology allows us to question and better understand our interactions with plants. In turn, this field opens the door to transdisciplinary projects with the society, notably through citizen science.Peer reviewe

Genotyping-by-sequencing-based identification of Arabidopsis pattern recognition receptor RLP32 recognizing proteobacterial translation initiation factor IF1

Activation of plant pattern-triggered immunity (PTI) relies on the recognition of microbe-derived structures, termed patterns, through plant-encoded surface-resident pattern recognition receptors (PRRs). We show that proteobacterial translation initiation factor 1 (IF1) triggers PTI in Arabidopsis thaliana and related Brassicaceae species. Unlike for most other immunogenic patterns, IF1 elicitor activity cannot be assigned to a small peptide epitope, suggesting that tertiary fold features are required for IF1 receptor activation. We have deployed natural variation in IF1 sensitivity to identify Arabidopsis leucine-rich repeat (LRR) receptor-like protein 32 (RLP32) as IF1 receptor using a restriction site-associated DNA sequencing approach. RLP32 confers IF1 sensitivity to rlp32 mutants, IF1-insensitive Arabidopsis accessions and IF1-insensitive Nicotiana benthamiana, binds IF1 specifically and forms complexes with LRR receptor kinases SOBIR1 and BAK1 to mediate signaling. Similar to other PRRs, RLP32 confers resistance to Pseudomonas syringae, highlighting an unexpectedly complex array of bacterial pattern sensors within a single plant species

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration ClinicalTrials.gov Identifier NCT0158936

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This study is being supported by grant no 04-2012-0290 from the SNUH Research fund and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP)(No. 2013005540). Letrozole and metformin are being supplied by the pharmaceutical company, Shin Poong Pharm. Co., Ltd.Background : Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design : Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion : This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration : ClinicalTrials.gov Identifier NCT01589367Peer Reviewe

Activation of the Arabidopsis thaliana Immune System by Combinations of Common ACD6 Alleles

A fundamental question in biology is how multicellular organisms distinguish self and non-self. The ability to make this distinction allows animals and plants to detect and respond to pathogens without triggering immune reactions directed against their own cells. In plants, inappropriate self-recognition results in the autonomous activation of the immune system, causing affected individuals to grow less well. These plants also suffer from spontaneous cell death, but are at the same time more resistant to pathogens. Known causes for such autonomous activation of the immune system are hyperactive alleles of immune regulators, or epistatic interactions between immune regulators and unlinked genes. We have discovered a third class, in which the Arabidopsis thaliana immune system is activated by interactions between natural alleles at a single locus, ACCELERATED CELL DEATH 6 (ACD6). There are two main types of these interacting alleles, one of which has evolved recently by partial resurrection of a pseudogene, and each type includes multiple functional variants. Most previously studies hybrid necrosis cases involve rare alleles found in geographically unrelated populations. These two types of ACD6 alleles instead occur at low frequency throughout the range of the species, and have risen to high frequency in the Northeast of Spain, suggesting a role in local adaptation. In addition, such hybrids occur in these populations in the wild. The extensive functional variation among ACD6 alleles points to a central role of this locus in fine-tuning pathogen defenses in natural populations

Genotyping-by-sequencing-based identification of Arabidopsis pattern recognition receptor RLP32 recognizing proteobacterial translation initiation factor IF1

https://doi.org/10.1038/s41467-022-28887-