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Frontiers in Plant Science 2018Switchgrass () is a native prairie grass and valuable bio-energy crop. The physiological change from juvenile to reproductive adult can draw important resources away...
Switchgrass () is a native prairie grass and valuable bio-energy crop. The physiological change from juvenile to reproductive adult can draw important resources away from growth into producing reproductive structures, thereby limiting the growth potential of early flowering plants. Delaying the flowering of switchgrass is one approach by which to increase total biomass. The objective of this research was to identify genetic variants and candidate genes for controlling heading and anthesis in segregating switchgrass populations. Four pseudo-F populations (two pairs of reciprocal crosses) were developed from lowland (late flowering) and upland (early flowering) ecotypes, and heading and anthesis dates of these populations were collected in Lafayette, IN and DeKalb, IL in 2015 and 2016. Across 2 years, there was a 34- and 73-day difference in heading and a 52- and 75-day difference in anthesis at the Lafayette and DeKalb locations, respectively. A total of 37,901 single nucleotide polymorphisms obtained by exome capture sequencing of the populations were used in a genome-wide association study (GWAS) that identified five significant signals at three loci for heading and two loci for anthesis. Among them, a homolog of FLOWERING LOCUS T on chromosome 5b associated with heading date was identified at the Lafayette location across 2 years. A homolog of ARABIDOPSIS PSEUDO-RESPONSE REGULATOR 5, a light modulator in the circadian clock associated with heading date was detected on chromosome 8a across locations and years. These results demonstrate that genetic variants related to floral development could lend themselves to a long-term goal of developing late flowering varieties of switchgrass with high biomass yield.
PubMed: 30271414
DOI: 10.3389/fpls.2018.01250 -
Proceedings of the National Academy of... Aug 2018The circadian clock coordinates the daily cyclic rhythm of numerous biological processes by regulating a large portion of the transcriptome. In animals, the circadian...
The circadian clock coordinates the daily cyclic rhythm of numerous biological processes by regulating a large portion of the transcriptome. In animals, the circadian clock is involved in aging and senescence, and circadian disruption by mutations in clock genes frequently accelerates aging. Conversely, aging alters circadian rhythmicity, which causes age-associated physiological alterations. However, interactions between the circadian clock and aging have been rarely studied in plants. Here, we investigated potential roles for the circadian clock in the regulation of leaf senescence in plants. Members of the evening complex in circadian clock, EARLY FLOWERING 3 (ELF3), EARLY FLOWERING 4 (ELF4), and LUX ARRHYTHMO (LUX), as well as the morning component PSEUDO-RESPONSE REGULATOR 9 (PRR9), affect both age-dependent and dark-induced leaf senescence. The circadian clock regulates the expression of several senescence-related transcription factors. In particular, PRR9 binds directly to the promoter of the positive aging regulator () gene to promote its expression. PRR9 also represses , a posttranscriptional repressor of Consistently, genetic analysis revealed that delayed leaf senescence of a mutant was rescued by overexpression. Thus, PRR9, a core circadian component, is a key regulator of leaf senescence via positive regulation of through a feed-forward pathway involving posttranscriptional regulation by and direct transcriptional regulation. Our results indicate that, in plants, the circadian clock and leaf senescence are intimately interwoven as are the clock and aging in animals.
Topics: Aging; Arabidopsis; Arabidopsis Proteins; Circadian Rhythm; MicroRNAs; Plant Leaves; Promoter Regions, Genetic; Transcription Factors
PubMed: 30065116
DOI: 10.1073/pnas.1722407115 -
The Plant Cell Apr 2018The rhythms of steady-state mRNA expression pervade nearly all circadian systems. However, the mechanisms behind the rhythmic transcriptional synthesis and its...
The rhythms of steady-state mRNA expression pervade nearly all circadian systems. However, the mechanisms behind the rhythmic transcriptional synthesis and its correlation with circadian expression remain fully unexplored, particularly in plants. Here, we discovered a multifunctional protein complex that orchestrates the rhythms of transcriptional activity in The expression of the circadian oscillator genes and initially relies on the modular function of the clock-related factor REVEILLE8: its MYB domain provides the DNA binding specificity, while its LCL domain recruits the clock components, NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED proteins (LNKs), to target promoters. LNKs, in turn, specifically interact with RNA Polymerase II and the transcript elongation FACT complex to rhythmically co-occupy the target loci. The functional interaction of these components is central for chromatin status, transcript initiation, and elongation as well as for proper rhythms in nascent RNAs. Thus, our findings explain how genome readout of environmental information ultimately results in rhythmic changes of gene expression.
Topics: Arabidopsis; Arabidopsis Proteins; Chromatin; Circadian Rhythm; Multiprotein Complexes; Promoter Regions, Genetic; RNA, Messenger; RNA, Plant
PubMed: 29618629
DOI: 10.1105/tpc.18.00052 -
Neuro-oncology Sep 2018ACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
ACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed glioblastoma. This study investigated whether changes in contrast-enhancing and fluid attenuated inversion recovery (FLAIR)-hyperintense tumor assessed by central reading prognosticate overall survival (OS).
METHODS
Two hundred eighty-four patients (171 men; median age 57 y, range 19-79; 159 on bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant temozolomide (22 wk post chemoradiation initiation). Four central readers measured bidimensional lesion enhancement (2D-T1) and FLAIR hyperintensity at both time points. Changes from baseline to pre-cycle 4 for both markers were dichotomized (increasing vs non-increasing). Cox proportional hazards model and Kaplan-Meier survival estimates were used for inference.
RESULTS
Adjusting for treatment, increasing 2D-T1 (n = 262, hazard ratio [HR] = 2.07, 95% CI: 1.48-2.91, P < 0.0001) and FLAIR (n = 273, HR = 1.75, 95% CI: 1.26-2.41, P = 0.0008) significantly predicted worse OS. Median OS (days) was significantly shorter for patients with increasing versus non-increasing 2D-T1 for both bevacizumab (443 vs 535, P = 0.004) and placebo (526 vs 887, P = 0.001). Median OS was significantly shorter for patients with increasing versus non-increasing FLAIR for placebo (595 vs 872, P = 0.001), and trended similarly for bevacizumab (499 vs 535, P = 0.0935). Adjusting for 2D-T1 and treatment, increasing FLAIR represented significantly higher risk for death (HR = 1.59 [1.11-2.26], P = 0.01).
CONCLUSION
Increased 2D-T1 significantly predicts worse OS in both treatment groups, implying absence of a substantial proportion of pseudoprogression 22 weeks after initiation of standard therapy. FLAIR adds value beyond 2D-T1 in predicting OS, potentially addressing the pseudoresponse effect by substratifying bevacizumab-treated patients with non-increasing 2D-T1.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Contrast Media; Double-Blind Method; Female; Follow-Up Studies; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Prognosis; Prospective Studies; Radiographic Image Enhancement; Retrospective Studies; Survival Rate; Temozolomide; Young Adult
PubMed: 29590461
DOI: 10.1093/neuonc/noy049 -
Current Biology : CB Jan 2018Plants coordinate their growth and development with the environment through integration of circadian clock and photosensory pathways. In Arabidopsis thaliana, rhythmic...
Plants coordinate their growth and development with the environment through integration of circadian clock and photosensory pathways. In Arabidopsis thaliana, rhythmic hypocotyl elongation in short days (SD) is enhanced at dawn by the basic-helix-loop-helix (bHLH) transcription factors PHYTOCHROME-INTERACTING FACTORS (PIFs) directly inducing expression of growth-related genes [1-6]. PIFs accumulate progressively during the night and are targeted for degradation by active phytochromes in the light, when growth is reduced. Although PIF proteins are also detected during the day hours [7-10], their growth-promoting activity is inhibited through unknown mechanisms. Recently, the core clock components and transcriptional repressors PSEUDO-RESPONSE REGULATORS PRR9/7/5 [11, 12], negative regulators of hypocotyl elongation [13, 14], were described to associate to G boxes [15], the DNA motifs recognized by the PIFs [16, 17], suggesting that PRR and PIF function might converge antagonistically to regulate growth. Here we report that PRR9/7/5 and PIFs physically interact and bind to the same promoter region of pre-dawn-phased, growth-related genes, and we identify the transcription factor CDF5 [18, 19] as target of this interplay. In SD, CDF5 expression is sequentially repressed from morning to dusk by PRRs and induced pre-dawn by PIFs. Consequently, CDF5 accumulates specifically at dawn, when it induces cell elongation. Our findings provide a framework for recent TIMING OF CAB EXPRESSION 1 (TOC1/PRR1) data [5, 20] and reveal that the long described circadian morning-to-midnight waves of the PRR transcriptional repressors (PRR9, PRR7, PRR5, and TOC1) [21] jointly gate PIF activity to dawn to prevent overgrowth through sequential regulation of common PIF-PRR target genes such as CDF5.
Topics: Arabidopsis; Arabidopsis Proteins; Basic Helix-Loop-Helix Transcription Factors; Circadian Clocks; Gene Expression Regulation, Plant; Photoperiod; Promoter Regions, Genetic; Transcription Factors
PubMed: 29337078
DOI: 10.1016/j.cub.2017.12.021 -
NPJ Precision Oncology 2017Precise assessment of treatment response in glioblastoma during combined anti-angiogenic and chemoradiation remains a challenge. In particular, early detection of...
Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival.
Precise assessment of treatment response in glioblastoma during combined anti-angiogenic and chemoradiation remains a challenge. In particular, early detection of treatment response by standard anatomical imaging is confounded by pseudo-response or pseudo-progression. Metabolic changes may be more specific for tumor physiology and less confounded by changes in blood-brain barrier permeability. We hypothesize that metabolic changes probed by magnetic resonance spectroscopic imaging can stratify patient response early during combination therapy. We performed a prospective longitudinal imaging study in newly diagnosed glioblastoma patients enrolled in a phase II clinical trial of the pan-vascular endothelial growth factor receptor inhibitor cediranib in combination with standard fractionated radiation and temozolomide (chemoradiation). Forty patients were imaged weekly during therapy with an imaging protocol that included magnetic resonance spectroscopic imaging, perfusion magnetic resonance imaging, and anatomical magnetic resonance imaging. Data were analyzed using receiver operator characteristics, Cox proportional hazards model, and Kaplan-Meier survival plots. We observed that the ratio of total choline to healthy creatine after 1 month of treatment was significantly associated with overall survival, and provided as single parameter: (1) the largest area under curve (0.859) in receiver operator characteristics, (2) the highest hazard ratio (HR = 85.85, = 0.006) in Cox proportional hazards model, (3) the largest separation ( = 0.004) in Kaplan-Meier survival plots. An inverse correlation was observed between total choline/healthy creatine and cerebral blood flow, but no significant relation to tumor volumetrics was identified. Our results suggest that in vivo metabolic biomarkers obtained by magnetic resonance spectroscopic imaging may be an early indicator of response to anti-angiogenic therapy combined with standard chemoradiation in newly diagnosed glioblastoma.
PubMed: 29202103
DOI: 10.1038/s41698-017-0020-3 -
Plant, Cell & Environment Dec 2017The relief of dormancy and the promotion of seed germination are of extreme importance for a successful seedling establishment. Although alternating temperatures and...
The relief of dormancy and the promotion of seed germination are of extreme importance for a successful seedling establishment. Although alternating temperatures and light are signals promoting the relief of seed dormancy, the underlying mechanisms of their interaction in seeds are scarcely known. By exposing imbibed Arabidopsis thaliana dormant seeds to two-day temperature cycles previous of a red light pulse, we demonstrate that the germination mediated by phytochrome B requires the presence of functional PSEUDO-RESPONSE REGULATOR 7 (PRR7) and TIMING OF CAB EXPRESSION 1 (TOC1) alleles. In addition, daily cycles of alternating temperatures in darkness reduce the protein levels of DELAY OF GERMINATION 1 (DOG1), allowing the expression of TOC1 to induce seed germination. Our results suggest a functional role for some components of the circadian clock related with the action of DOG1 for the integration of alternating temperatures and light signals in the relief of seed dormancy. The synchronization of germination by the synergic action of light and temperature through the activity of circadian clock might have ecological and adaptive consequences.
Topics: Arabidopsis; Arabidopsis Proteins; Circadian Clocks; Cues; Germination; Phytochrome B; Plant Dormancy; Repressor Proteins; Seedlings; Seeds; Temperature; Transcription Factors
PubMed: 28941290
DOI: 10.1111/pce.13076 -
Scientific Reports Aug 2017Calcium signalling mediated by Calmodulin (CaM) and calmodulin-like (CML) proteins is critical to plant immunity. CaM and CML regulate a wide range of target proteins...
Calcium signalling mediated by Calmodulin (CaM) and calmodulin-like (CML) proteins is critical to plant immunity. CaM and CML regulate a wide range of target proteins and cellular responses. While many CaM-binding proteins have been identified, few have been characterized for their specific role in plant immunity. Here, we report new data on the biological function of a CML-interacting partner, PRR2 (PSEUDO-RESPONSE REGULATOR 2), a plant specific transcription factor. Until now, the physiological relevance of PRR2 remained largely unknown. Using a reverse genetic strategy in A. thaliana, we identified PRR2 as a positive regulator of plant immunity. We propose that PRR2 contributes to salicylic acid (SA)-dependent responses when challenged with the phytopathogenic bacterium Pseudomonas syringae. PRR2 is transcriptionally upregulated by SA and P. syringae, enhances SA biosynthesis and SA signalling responses; e.g. in response to P. syringae, PRR2 induces the production of SA and the accumulation of the defence-related protein PR1. Moreover, PRR2 overexpressing lines exhibit an enhanced production of camalexin, a phytoalexin that confers enhanced resistance against pathogens. Together, these data reveal the importance of PRR2 in plant immune responses against P. syringae and suggest a novel function for this particular plant specific transcription factor in plant physiology.
Topics: Arabidopsis; Arabidopsis Proteins; Calcium Signaling; Carrier Proteins; Disease Resistance; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Indoles; Plant Diseases; Plants, Genetically Modified; Pseudomonas syringae; Reverse Genetics; Salicylic Acid; Thiazoles; Up-Regulation
PubMed: 28765536
DOI: 10.1038/s41598-017-07535-8 -
Journal of Clinical Oncology : Official... Jul 2017Development of novel therapies for CNS tumors requires reliable assessment of response and progression. This requirement has been particularly challenging in... (Review)
Review
Development of novel therapies for CNS tumors requires reliable assessment of response and progression. This requirement has been particularly challenging in neuro-oncology for which contrast enhancement serves as an imperfect surrogate for tumor volume and is influenced by agents that affect vascular permeability, such as antiangiogenic therapies. In addition, most tumors have a nonenhancing component that can be difficult to accurately quantify. To improve the response assessment in neuro-oncology and to standardize the criteria that are used for different CNS tumors, the Response Assessment in Neuro-Oncology (RANO) working group was established. This multidisciplinary international working group consists of neuro-oncologists, medical oncologists, neuroradiologists, neurosurgeons, radiation oncologists, neuropsychologists, and experts in clinical outcomes assessments, working in collaboration with government and industry to enhance the interpretation of clinical trials. The RANO working group was originally created to update response criteria for high- and low-grade gliomas and to address such issues as pseudoresponse and nonenhancing tumor progression from antiangiogenic therapies, and pseudoprogression from radiochemotherapy. RANO has expanded to include working groups that are focused on other tumors, including brain metastases, leptomeningeal metastases, spine tumors, pediatric brain tumors, and meningiomas, as well as other clinical trial end points, such as clinical outcomes assessments, seizures, corticosteroid use, and positron emission tomography imaging. In an effort to standardize the measurement of neurologic function for clinical assessment, the Neurologic Assessment in Neuro-Oncology scale was drafted. Born out of a workshop conducted by the Jumpstarting Brain Tumor Drug Development Coalition and the US Food and Drug Administration, a standardized brain tumor imaging protocol now exists to reduce variability and improve reliability. Efforts by RANO have been widely accepted and are increasingly being used in neuro-oncology trials, although additional refinements will be needed.
Topics: Central Nervous System Neoplasms; Clinical Trials as Topic; Disease Progression; Humans; Neuroimaging; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Quality of Life; Tumor Burden
PubMed: 28640707
DOI: 10.1200/JCO.2017.72.7511