Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Therefore, the observed effects of HIPK2 on p53 seem to be mediated by Mdm2. We conclude that an important function of HIPK2 is the stabilization and activation of p53 by inducing degradation of Mdm2. ResultsHIPK2 activates p53-mediated transcriptionSince HIPK2 has been described as a nuclear protein that interacts with homeodomain containing transcription factors [9, 11], we looked for an influence of HIPK2 on transcription mediated by several transcription factors such as p53, NFκB and Elk1. The tumorsuppressor p53 is a transcription factor that binds to DNA and is involved in the cell cycle and apoptosis. To test a possible transcriptional transactivation activity of HIPK2, expression vectors encoding wildtype or the mutated HIPK2 proteins (AC, AN and K221A) were transfected into 293 (Fig. 1A) and HeLa (Fig. 1B) cells together with p53-luc, a luciferase reporter gene under the control of the p53-specific enhancer element ()15. The p53-specific enhancer element is derived from the sequence comparison of promoters of p53-inducible genes [12, 13]. HeLa cells have been found to contain endogenous transcriptionally active p53 protein by the intrinsic ability to transactivate p53-responsive promoter elements [14]. In line with this, endogenous p53 of the HeLa cells used in our experiments had transcriptional activity and wildtype sequence (data not shown). Activation of the luciferase activity by cotransfection of 50 ng of the reporter plasmid encoding p53 (pFC-p53) was 250 fold for 293 and 160 fold for HeLa cells, respectively (data not shown). The luciferase value of vector and p53-luc transfected cells were standardized for a value of 1 in each assay, to control for activation of the p53 specific enhancer element by endogenous p53. The intrinsic activity of endogenous p53 was approximately 20 fold above the blank controls (data not shown). Wildtype HIPK2 induced a 40 fold increase of p53-mediated transcription in 293 cells compared to the increase in vector transfected control cells (Fig. 1A). [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the effects of HIPK2 on p53 in a cellular context and does not mention urban living or stress levels. Therefore, it neither supports nor contradicts the claim.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: 62b 7. 53fg 11. 36 25. 36gh 73. 26c 7. 48ef 11. 41 25. 15fg S2T3 76. 62b 7. 34g 11. 43 25. 02i 77. 53b 7. 29f 11. 48 24. 98gh S3T0 60. 51ef 8. 51bc 11. 12 26. 33bc 60. 26fg 8. 35bc 11. 15 26. 05bc S3T1 70. 22c 7. 62fg 11. 33 25. 52fg 72. 21c 7. 53ef 11. 38 25. 51def S3T2 74. 36b 7. 45g 11. 40 25. 13hi 76. 62b 7. 36ef 11. 45 25. 06g S3T3 81. 36a 6. 38h 11. 52 24. 65j 82. 65a 6. 31g 11. 57 24. 59h LSD0. 05 3. 09 0. 39 0. 15 0. 28 2. 76 0. 40 0. 158 0. 41 S1 = Aerobic Rice, S2 = Alternative wetting and drying (Transplanted), S3 = Flooded (Transplanted), T0 = Control, T1 = Boron (0. 1%), T2 = NAA (40 µmol L− 1), T3 = B + NAA (50%, 50%). Grain cooking quality parameters Foliar application of NAA and Boron provided remarkable results to uplift rice cooking quality. Results revealed that T3 produced 9. 82, 9. 68% longer grains, improved 30. 51, 29. 81% grain breadth and 23. 74, 23. 94% grain thickness in flooded cultivation system (S3) during both the consecutive years i. e. 2018, 2019 when we compare it with S1T0. Similarly this application i. e. T3 also improved 8. 63, 8. 60% grain length, 27. 70, 26. 14% grain breadth and 21. 48, 20. 58% grain thickness in AWD (S2) in 2018 and 2019. Moreover, in aerobic this application (T3) only enhanced 4. 31, 4. 16% grain length, 23. 57, 19. 85% grain breadth and 11. 66, 11. [SEP] Justify:

Output: The text corroborates the claim by providing specific examples of how certain treatments, such as the foliar application of NAA and Boron, led to significant improvements in rice cooking quality parameters. It details the percentage increases in grain length, breadth, and thickness, demonstrating that the modifications can indeed enhance the crop yield and improve its nutritional qualities.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: 1186/s12864-017-4412-0)| falseSearch 20. . Ethics, genetic testing, and athletic talent: children’s best interests, and the right to an open (athletic) future. Physiol Genomics. 2016;48(3):191–195. PubMed ID: 26757798 doi:10. 1152/physiolgenomics. 00104. 2015. Ethics, genetic testing, and athletic talent: children’s best interests, and the right to an open (athletic) future. Physiol Genomics. 2016;48(3):191–195. PubMed ID: 26757798 doi:10. 1152/physiolgenomics. 00104. 201510. 1152/physiolgenomics. 00104. 2015)| falseSearch 21. . Can genetic testing identify talent for sport? Genes. 2019;10(12):972. doi:10. 3390/genes10120972. Can genetic testing identify talent for sport? Genes. 2019;10(12):972. doi:10. 3390/genes1012097210. 3390/genes10120972)| falseSearch 22. Niemi AK, Majamaa K. Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Hum Genet. 2005;13(8):965–969. PubMed ID: 15886711 doi:10. 1038/sj. ejhg. 5201438. Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Hum Genet. 2005;13(8):965–969. PubMed ID: 15886711 doi:10. 1038/sj. ejhg. 52014381588671110. 1038/sj. ejhg. 5201438)| falseSearch 23. . Mitochondrial haplogroup T is negatively associated with the status of elite endurance athlete. Mitochondrion. 2007;7(5):354–357. PubMed ID: 17660050 doi:10. 1016/j. mito. 2007. 06. 002. Mitochondrial haplogroup T is negatively associated with the status of elite endurance athlete. Mitochondrion. [SEP] Justify:

Output: The text discusses ethical considerations and limitations of genetic testing, indicating that it is not infallible and does not predict all possible future health problems. This directly contrasts with the claim that genetic testing can provide absolute certainty regarding health outcomes.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: No such strong increase was observed with the kinase defective HIPK2 mutant K221A, a carboxy-terminal HIPK2 deletion mutant AC or an amino-terminal deletion mutant AN (Fig. 1A and 1B). But luciferase activity induced by the HIPK2 mutants was above the vector controls. Protein expression of recombinant HIPK2 in HeLa cells was shown in Western analysis after transient transfection of a Flag-tagged wildtype HIPK2 expression construct as described [26] (Fig. 1D). Expression of overexpressed and endogenous HIPK2 protein in HeLa cells was not detected by using a polyclonal anti-HIPK2 antiserum [26] (data not shown). Figure 1Activation of p53-mediated transcription by HIPK2 overexpression. 293 (A), HeLa (B) and Saos2 (C) cells were cotransfected with a p53-luciferase reporter construct and the indicated HIPK2 constructs or vector. Results represent the mean of three independent experiments. Bars, SD. (D) Western analysis of transient overexpression of Flag-tagged wildtype HIPK2 in HeLa cells (right lane) compared to vector-transfected control cells (left lane) with an anti-Flag antibody. Full size image To test whether HIPK2 activates transcription mediated by p53 responsive elements via p53, we transiently transfected human Saos2 cells, which lack p53 expression [15], with different HIPK2 expression constructs (Fig. 1C). Expression of wildtype HIPK2 did not lead to a significant increase in luciferase activity compared to its mutants, K221A and AC, and the vector control. However, transfection of 50 ng of pFC-p53 into Saos2 cells resulted in a 200 fold increase in luciferase activity and this increase was not further enhanced in the presence of HIPK2 (data not shown). Taken together, HIPK2 activates transcription mediated by p53 specific promoter elements and p53 is required for this effect. The enhancement of transcription is diminished by different mutations of HIPK2. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the effects of HIPK2 mutants on transcriptional activity related to p53 without addressing urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: 49b 1. 47b 1. 83 1. 33bc 7. 50c 1. 50bc 1. 86 1. 31c S3T3 7. 63a 1. 54a 1. 93 1. 39a 7. 64a 1. 61a 1. 90 1. 42a LSD0. 05 0. 07 0. 05 0. 45 0. 05 0. 05 0. 04 0. 10 0. 05 S1 = Aerobic Rice, S2 = Alternative wetting and drying (Transplanted), S3 = Flooded (Transplanted), T0 = Control, T1 = Boron (0. 1%), T2 = NAA (40 µmol L− 1), T3 = B + NAA (50%, 50%). Boron and Auxin analysis The analysis of samples disclosed that all treatments were responsive to boron application. The treatments where boron was applied depicted more boron contents in respective cultivation systems. Results further indicated that T1 produced 20. 41, 23. 01% more boron contents during 2018 and 2019 in flooded conditions (S3) while comparing with S1T0. Likewise this T1 revealed 17. 48, 20. 76% higher boron contents in both the years (2018, 2019) in the crop grown in AWD (S2) as compared to S1T0. Furthermore the T1 application depicted 16. 19, 19. 82% more boron contents than S1T0 in respective years (2018, 2019) in aerobic cultivation system. The results revealed that application of naphthalene acetic acid (NAA) proved helpful to increase auxin levels in all cultivation systems. It was evident that T2 supplied 67. 17, 58. 45% higher auxin contents in S3 (Flooded cultivation system) S1T0 during both studied years (2018, 2019). Similarly T2 also raised 62. 65, 53. 12% more auxin contents than S1T0 in alternative wetting and drying (S2) in consecutive years i. e. 2018 and 2019. Additionally in aerobic cultivation system (S1) the T2 application amplified 55. 50, 44. 39% auxin contents in comparison with S1T0 during 2018 and 2019 respectively (Fig-2). Economic analysis All expenses involved in crop cultivation were noted and were compared with the final income. [SEP] Justify:

Output: The text corroborates the claim by detailing the effects of boron and NAA treatments on crop cultivation systems, specifically indicating that these treatments resulted in significant increases in boron and auxin contents in various cultivation conditions. For example, it states that the application of boron produced more boron contents in flooded conditions and alternative wetting and drying systems when compared to controls, thereby illustrating precise modifications made to enhance nutrient content. Similarly, the text indicates that the NAA treatment increased auxin levels significantly in all cultivation systems, which supports the claim regarding improvements in nutrient content and potentially crop yield.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: 2007;7(5):354–357. PubMed ID: 17660050 doi:10. 1016/j. mito. 2007. 06. 00210. 1016/j. mito. 2007. 06. 002)| falseSearch 24. Mitochondrial haplogroups associated with elite Kenyan athlete status. Sports Exerc. 2009;41(1):123–128. PubMed ID: 19092698 doi:10. 1249/MSS. 0b013e31818313a2 Mitochondrial haplogroups associated with elite Kenyan athlete status. Sports Exerc. 2009;41(1):123–128. PubMed ID: 19092698 doi:10. 1249/MSS. 0b013e31818313a210. 1249/MSS. 0b013e31818313a219092698)| falseSearch 25. Association between COMT Val158Met polymorphism and competition results of competitive swimmers. J Sports Sci. 2018;36(4):393–397. PubMed ID: 28368213 Association between COMT Val158Met polymorphism and competition results of competitive swimmers. J Sports Sci. 2018;36(4):393–397. PubMed ID: 2836821328368213)| falseSearch 26. The relationship between personality traits, the 5HTT polymorphisms, and the occurrence of anxiety and depressive symptoms in elite athletes. PLoS One. 2016;11(6):e0156601. PubMed ID: 27257942 doi:10. 1371/journal. pone. 0156601 The relationship between personality traits, the 5HTT polymorphisms, and the occurrence of anxiety and depressive symptoms in elite athletes. PLoS One. 2016;11(6):e0156601. PubMed ID: 27257942 doi:10. 1371/journal. pone. 01566012725794210. 1371/journal. pone. 0156601)| falseSearch 27. Marouli E, Graff M, Medina-Gomez C, et al. Rare and low-frequency coding variants alter human adult height. Nature. 2017;542(7640):186–190. PubMed ID: 28146470 doi:10. 1038/nature21039-Gomez C, et al. [SEP] Justify:

Output: The text does not provide any direct evidence to support the claim that genetic testing can predict all future health problems with absolute certainty. Instead, it discusses various studies related to genetic polymorphisms, athlete performance, and personality traits without confirming the absolute predictive capability of genetic testing for health issues. Therefore, it contrasts with the claim by suggesting that genetic testing judgments are not definitive.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Wildtype HIPK2 leads to an increase of p53 expression or stabilitySince HIPK2 activated p53-mediated transcription, we looked whether HIPK2 leads to an increase in the level of p53 protein after transient transfection of HeLa cells. Wildtype HIPK2 enhanced protein expression or stability of p53 compared to the vector transfected controls (Fig. 2A). The kinase-defective mutant K221A and the amino-terminal deletion AN which lacks the kinase domain led to a decrease of p53 protein. The carboxy-terminal HIPK2 deletion mutant AC which contains the kinase part did not influence p53 protein levels (Fig. 2A). This is a hint that the increase of p53 protein induced by wildtype HIPK2 could be responsible for the enhanced transcriptional activity mediated by p53 binding promoter elements (Fig. 1). Figure 2Enhancement of p53 protein levels by wildtype HIPK2. HeLa cells were transiently transfected with the indicated HIPK2 expression constructs. Cellular extracts were analyzed for p53 expression by Western blotting. The signals corresponding to p53 or phosphorylated p53 (Phospho-p53) are indicated by an arrow. Equal loading was confirmed by reprobing the blots with an anti-β-actin antibody as shown below. (A) Cells were left untreated after transfection. (B) 24 h after transfection, doxorubicin was added to a final concentration of 0. 1 μg/ml for 3 and 6 h as indicated. (C) 24 h after transfection doxorubicin was added to a final concentration of 0. 1 μg/ml for 6 h and anti-phospho-p53 (Ser 15)-antibody was used for detection of phosphorylated serine 15 in p53. wt, wildtype; vec, vector. Full size image Doxorubicin enhances the HIPK2-mediated increase of p53 expression or stabilitySince p53 is stabilized in response to DNA damage, we tested whether HIPK2 has an effect on stabilization of p53 mediated by the DNA damaging drug doxorubicin in HeLa cells. Doxorubicin induced a significant increase of the p53 protein level after 6 h in the vector-transfected controls (Fig. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the effects of wildtype HIPK2 on p53 expression in relation to cellular responses and drug treatment, without any mention of urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: 87 S1 = Aerobic Rice, S2 = and drying (Transplanted), S3 = Flooded (Transplanted), T0 = Control, T1 = Boron (0. 1%), T2 = NAA (40 µmol L− 1), T3 = B + NAA (50%, 50%). DiscussionThis two-year study showed that that NAA and B application improved the rice physiological mechanism which in turn resulted as better crop productivity in term of yield and quality. Climate is very uncertain in these days which has its typical impact on crop production every year. Reproductive stage is very crucial in all crops which should be managed properly for better crop yield. Pakistan is drastically affecting with climate change, as every year farmer losses the crop yields due to uncertain rainfall, sudden temperature rise, hail storming etc. rice is also very sensitive to temperature especially at reproductive or grain formation stage. Due to changing rainfall pattern and uneconomical performance of cotton crop, farmers are preferring rice crop in southern Punjab although have high temperature. It’s under observation that every year rice crop faced high temperature at its reproductive which causes fertilization and increased sterility. Heat stress at flowering induces spikelet sterility by inhibiting pollen tube germination and pollen tube elongation (Aryan et al. , 2023; Sinder et al. , 2011). Moreover, the sporogenesis process is affected which resulted in spikelet sterility (Parish et al. , 2012). Its reported that exogenous application of auxin and Boron improve the sporogenesis process and pollen viability is rice crop (Sharma et al. , 2018; Rehman et al. , 2014). In this study it was found that both boron and NAA application improve the normal kernels and reduced the sterile grains. Similarly, grains produced with application of NAA and B also resulted in better cooking quality which is important character for larger export. As mentioned earlier that growing conditions are key factor to acquire best quality grains so flooding conditions and AWD were equally good regarding cooking quality which is also amplified by the addition of boron and naphthalene acetic acid into plant system. Improved grain quality and reduction in sterile grains, might be the result of better physiological mechanism of the plant which enhanced the pollen viability. Improved level of auxin also helps plant to uptake optimum amount of nutrients (Kurpea and Smalle, 2020). [SEP] Justify:

Output: The text corroborates the claim by stating that 'the application of NAA and B improved the rice physiological mechanism which in turn resulted as better crop productivity in term of yield and quality.' This indicates that specific modifications in the treatment of the crop can lead to improved yield and quality, aligning directly with the claim about precise modifications enhancing crop yield and nutrient content.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: to save searches and organize your favorite content. Not registered? Sign up (0) Recently viewed (0) Searches (0) Recently viewed (0) -mail the of the 360 Call for a for Authors Reprints/(FKA Harborside) in of Testing: a Role for With Cancer? Authors: Ying L. L. Genetics Service, Department of. Search for other papers by Ying L. Liu inCurrent site10. 6004/jnccn. 2021. 7044 Full access to Print Abstract/1. Pros and cons of tumor-only versus paired tumor-normal genetic testing. This figure depicts the results of germline, tumor, and paired tumor-normal sequencing and displays how paired sequencing allows the differentiation of germline (red) versus somatic (blue) results. Abbreviation: MSI, microsatellite instability. Citation: Journal of the 19, 7; 10. 6004/jnccn. 2021. 7044The advantage of a tumor-only approach is efficiency, because germline DNA is not directly interrogated, and the necessary informed consents, privacy protections, and pretesting/posttesting genetic counseling inherent to traditional germline genetic testing are not routinely needed. 14,15 For the identification of therapeutically actionable genetic mutations, knowledge of the origin of the mutation as somatic versus germline is not always necessary. In addition, novel computational algorithms may eventually facilitate the accurate identification of somatic versus germline variants from tumor testing alone, raising the possibility of the return of germline results in the context of appropriate pretest informed consent. 16The disadvantages include challenges to the interpretation of results and the need for additional germline testing in certain patients, which could lead to delays in management and cascade testing. For example, tumor-only testing of a breast cancer sample may identify a BRCA1/2 mutation, but it is unclear whether this mutation is somatic or germline. Additional genetic testing would be necessary but could potentially delay decisions regarding surgical management (mastectomy vs lumpectomy) and notification of at-risk relatives. Notably, negative tumor-only testing is not an adequate surrogate for dedicated germline testing, especially when the implications for cancer surveillance, treatment, and cascade testing are so critical. As recently shown by Lincoln et al,17 8. [SEP] Justify:

Output: The text contrasts the claim by highlighting the limitations of tumor-only genetic testing and the necessity of additional germline testing for accurate predictions. It mentions that 'negative tumor-only testing is not an adequate surrogate for dedicated germline testing,' indicating that genetic testing does not always provide absolute certainty about future health problems, especially in the context of identifying specific mutations and their origins.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: 2B). When cells were transiently transfected with wildtype HIPK2, the increase of p53 protein was similar to that observed after 6 h doxorubicin treatment. The combination of overexpression of HIPK2 and treatment with doxorubicin for 6 h resulted in an increase in p53 protein levels compared to either treatment alone, i. e. the HIPK2-mediated increase of the p53 protein level was further enhanced by the addition of doxorubicin (Fig. 2B). In summary, these results show that wildtype HIPK2 but not kinase deficient or severely truncated mutants led to an increase of p53 protein. Treatment with doxorubicin for at least 6 h further increased the amount of p53 protein. HIPK2 is not sufficient for phosphorylation of serine 15, serine 20 and serine 392 of p53Since HIPK2 contains a serine/threonine kinase domain and since multiple serine/threonine phosphorylation sites are present in p53 protein, we used antibodies that specifically detect single phosphorylated serine residues of p53 to look for a putative HIPK2-mediated phosphorylation of p53. Upon treatment with doxorubicin, serine 15 is phosphorylated in HeLa cells (Fig. 2C). However, no serine 15 phosphorylation was detected after transient transfection of HIPK2 in the absence of doxorubicin treatment. The amount of phosphorylated protein after doxorubicin treatment reflects the total amount of p53 protein (Fig. 2A, B and 2C), which suggests that almost all p53 protein present became phosphorylated on serine 15. Since the kinase defective HIPK2 mutant K221A probably acts in a dominant negative way, the amount of p53 which was induced by endogenous HIPK2 in the vector-transfected controls decreased. Similar to the decrease in the amount of p53 protein in the presence of the K221A mutant (Fig. 2A) there was a decrease in phosphorylated p53 after treatment with doxorubicin (Fig. 2C). [SEP] Justify:

Output: The text is irrelevant to the claim about urban living and stress levels, as it focuses on biochemical reactions related to HIPK2 and p53 protein rather than any aspects of living conditions, mental stress, or urban environments.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: Similarly, boron has the ability to provide better growth to plant as it improves the physiological and biological processes of the plant (Shahid et al. , 2018; García-Hernández and López, 2005). It was observed that rice crop improved the gasses exchange system to optimize the photosynthetic system in all cultivation system under NAA & B application while the effect was super most in well-watered condition. Previous studies also concluded that naphthalene acetic acid not only modulates plant gas exchange but also improves plant growth (Hao et al. , 2011; Bauly et al. , 2000). Likewise, Sarwar et al. (2019) emphasizes that NAA reduces panicle infertility which helps plant in proper grain development. Results revealed that crop grown under less water condition and without application of NAA & B reduced the crop yield while there was substantial increase recorded with application of pre-mentioned amendments. Overall, the application improved the crop physiological mechanism which enhanced the crop yield in term of 1000-grain weight. Positive effect was noted across all different cultivation systems while the flooded and AWD were found prominent. Observation suggest that application of NAA and B alleviate the high temperature stress at flowering stage by improving the contents of auxin and boron within plant and improve crop yield. The improved boron in plant system helped to get better growth, maximum yield and quality (Arif et al. , 2012). Similarly, it’s also verified that application of NAA and boron, also found economical which most important parameter is for farmers especially in developing countries. In this local region, farmer adoption is greatly dependant on economics so experiment highlighted after recording all expenses and benefit that its economically sound way of cultivation. ConclusionNAA and boron application before flowering found a use full strategy to manage the abiotic stresses which improve the pollen viability and enhanced the healthy grains in different cultivation systems. Moreover, this application also improves the cooking quality of rice grain which is most desired character for its export and local consumption. Similarly, it was also proved economically sustained which may encourage farmer adoption. authors have no competing interests to declare that are relevant to the content of this 1597. (2012) Boron and zinc microtone effects on growth, chlorophyll contens and yield attributes in rice. Biotech 11(48): 10851-10858. [SEP] Justify:

Output: The text corroborates the claim by detailing how the application of boron and naphthalene acetic acid (NAA) leads to improved growth and increased crop yield. It specifically mentions that the introduction of these substances enhances the physiological mechanisms of crops and optimizes their physiological and biological processes, resulting in better gas exchange and ultimately higher yields. The text states, 'Overall, the application improved the crop physiological mechanism which enhanced the crop yield in term of 1000-grain weight,' supporting the idea that precise modifications can improve both crop yield and nutrient content.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: 1% of pathogenic germline mutations were missed in patients who previously underwent tumor-only sequencing because of the technical limitations of tumor sequencing, variant interpretation differences, or differences in the genes tested in the tumor versus the germline. Perhaps most importantly, in tumor-only testing, the germline nature of findings may be misinterpreted by providers inexperienced in cancer genetics or incorrectly relayed to patients, resulting in suboptimal care not only for the patient but also for at-risk family members. 18 As a result, the of and Genomics19 and NCCN20 have issued guidelines for the reporting of potential germline variants from tumor testing, and laboratories and clinicians should receive guidance and training on interpreting tumor-only testing and potential germline findings. 21,22 Even in tumor-only testing, multidisciplinary care is often necessary to identify potential germline variants and facilitate genetic counseling and confirmatory germline testing. 19,21–23The advantage of parallel tumor-normal testing is that it provides an unbiased assessment of the germline and somatic contribution to cancer risk and development. 10 It also allows the integration of tumor and normal genomic data and complex interpretation, including the evaluation of loss of heterozygosity in tumor tissues and the differentiation of mosaicism and clonal hematopoiesis, which have implications for the heritability of findings. 10 From a technical standpoint, it allows sample verification and additional quality control checks and may provide insight into the classification of germline variants. 24Disadvantages include the extra costs, resources, and expertise that are necessary for the successful implementation, interpretation, and dissemination of results. There also need to be mechanisms in place for the timely and comprehensive management of any germline findings. In addition, the identification of “incidental” germline findings may be the double-edged sword of parallel tumor-normal testing. Although such germline findings may better elucidate cancer risk in families, the uncertainty of cancer risk estimates or gene penetrance in families without the corresponding phenotypic features make management decisions difficult, particularly in situations where risk-reducing surgeries may be relevant. For example, in a patient without a family history of gastric or lobular breast cancer, an incidental finding of a CDH1 germline mutation on parallel testing makes decisions regarding prophylactic gastrectomy extremely difficult. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations of genetic testing, particularly tumor-only sequencing and its challenges in identifying germline mutations. It emphasizes that genetic testing does not offer absolute certainty in predicting health problems due to various factors such as technical limitations, misinterpretation of germline findings, and the complexities involved in managing incidental findings. Therefore, the assertion that genetic testing can predict all future health problems with absolute certainty is undermined by the evidence presented.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: As expected from these findings, overexpression of the HIPK2 mutants AN and AC yielded less phosphorylated p53 compared to overexpression of wildtype HIPK2 in the presence of doxorubicin (Fig. 2C). Similar results were obtained using an antibody against serine residue 20 (data not shown). Using an antibody that specifically detects phosphorylation of serine 392 in p53 we could not detect phosphorylated p53 either in the presence of doxorubicin or during overexpression of HIPK2 (data not shown). Taken together, HIPK2 is not sufficient for phosphorylation of p53 at serine residues 15 and 20, where doxorubicin seems to be required, and for phosphorylation of serine 392. HIPK2 leads to a decrease of p53-induced Mdm2 expressionTo further characterize the interaction of HIPK2 and p53, Saos2 cells were transiently cotransfected with constructs coding for p53, p53 and wildtype HIPK2 or p53 and the kinase defective HIPK2 mutant K221A together with pEGFP-Nl coding for a green fluorescence protein (Fig. 3A). Mdm2 and p53 proteins were not detectable in Saos2 cells (lane 1). In agreement with previous observations [16, 17], wildtype p53 led to an induction of endogenous Mdm2 expression (lane 2). Interestingly, a p53-mediated induction of Mdm2 expression was not observed in the presence of wildtype HIPK2 (lane 3). Therefore, HIPK2 overexpression led to a decrease of p53-induced Mdm2 protein levels. This decrease in Mdm2 protein was not observed by coexpression of the kinase defective HIPK2 mutant K221A (lane 4), which suggests that the kinase domain is necessary for Mdm2 downregulation. Equal protein loading was shown by reprobing the filters with an antibody detecting β-actin. pAGFP-Nl was cotransfected in all cases to normalize overexpression. GFP fluorescence was not significantly different (Fig. 3B), indicating similar transfection efficiencies. Figure 3Downregulation of p53-induced Mdm2 by overexpressed HIPK2. [SEP] Justify:

Output: The text does not relate to the claim about urban living and stress levels. It discusses the biological interactions between HIPK2 and p53 in a scientific context, particularly focusing on protein phosphorylation and related experiments, which have no connection to stress levels or urban living.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: (2023) Auxin application at the flowering stage of rice alleviates the negative impact of heat stress on spikelet fertility and yield attributes. Agri 13: 866. (2011) Effect of Naphthalene acetic acid and phosphorus levels on yield potential of transplanted coarse rice. Agric 27(2): 161-165. (2000) Over expression of auxin binding protein enhances sensitivity of guard cells to auxin. 124: 1229-1238. (2013) Research paradigm and inference of studies on high temperature stress in rice (Oryza sativa L. ). Advances in. Hemantaranjan A, Scientific Publishers. 497-11. (2018) Impact of high temperature stress during reproductive and grain filling stage in rice. ORYZA-An. Rice 55(1): 126-33. Calderón-Páez SE, Cueto-Niño YA, Sánchez-Reinoso AD, Garces-Varon G, Chávez-Arias CC, Restrepo-Díaz H (2021) Foliar boron compounds applications mitigate heat stress caused by high daytime temperatures in rice (Oryza sativa L. ) Boron mitigates heat stress in rice. J 44(17): 2514-2527. (2016) Estimation of gas exchange parameters in back cross introgressed lines of rice (Oryza sativa L. ) with different combinations of drought QTLs. Res 18(2): 106-114. FAO (Food and of the United Nations). 2022. World: Rice, Quantity [2021-12-24]. (2012) Thermal resistance of common rice maintainer and restorer lines to high temperature during flowering and early grain filling stage. 19: 309-314. García-Hernández ER, López GIC (2005) Structural cell wall proteins from five pollen species and their relationship with boron. 17:375–381. (2011) Salicylic acid induces stomatal closure by modulating endogenous hormone level in cucumber cotyledon. 58: 906-913. Hossain, ABMS (2023) Influence of Acid on the Fruit Growth, Chlorophyll, pH and in Rose Apple. 2(1): 01-08. [SEP] Justify:

Output: The text corroborates the claim by discussing various studies that highlight the impact of auxin application and other interventions on crop yield and the alleviation of heat stress in rice, which directly relates to improving crop yield and nutrient content. For example, it mentions 'Auxin application at the flowering stage of rice alleviates the negative impact of heat stress on spikelet fertility and yield attributes,' indicating how precise modifications can indeed enhance yield.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: 25,26the advent of tumor-normal testing, more clinically actionable germline findings are being discovered across cancer types, often in patients who do not meet traditional criteria for genetic testing. 27 In a study of 1,566 patients with paired tumor-normal testing using a 341-gene panel (),6 246 patients (15. 7%) had at least 1 pathogenic or likely pathogenic variant in 1 of 187 Mendelian disease-associated genes. 28 A subsequent study examined 10,336 patients who underwent tumor-normal sequencing with of which 1,040 were consented for germline analysis including 76 cancer-predisposing genes. Of these patients, 182 (17. 5%) had clinically actionable variants conferring cancer susceptibility. Notably, 101, or 55% of germline-positive patients, would not have met the clinical criteria for guideline-based genetic testing. 29 Two smaller studies found that rates of discovery of pathogenic germline variants in patients with paired tumor-normal genetic testing were slightly lower, ranging from 2. 3% to 4. 3%. 30,31 In the largest study, Huang et al32 used an automatic germline variant classification pipeline (CharGer) to analyze 10,389 patients who underwent tumor-normal testing from and found that 853 patients (8%) had pathogenic or likely pathogenic germline variants (Table 1). Table 1. Rates of in Parallel Tumor-for Predisposition SyndromesParallel sequencing provides opportunities for the discovery of novel genes and predisposition syndromes in many new cancer types. In a study of 451 patients with locally advanced or metastatic prostate cancer who underwent parallel sequencing, germline findings were available in a subset of 221 patients, of whom 42 (19%) had pathogenic/likely pathogenic germline mutations in DNA damage repair genes. 33 In a study of 254 patients with renal cell carcinoma who underwent paired sequencing, 41 (16. 1%) had germline mutations. Several of these patients (n=5) would not have met the clinical guidelines for genetic testing. In addition, an overrepresentation of CHEK2 mutations was seen, suggesting a potentially novel association. 34 A similar study conducted in 586 patients with urothelial cancers, which are traditionally associated with mismatch repair deficiency (MMR-D) and Lynch syndrome, identified 54 individuals (9. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations of genetic testing. It highlights studies where patients with cancer had actionable genetic variants, but notably points out that many of these patients did not meet traditional criteria for genetic testing. This suggests that while genetic testing can provide some insights into possible health risks, it does not guarantee the prediction of all future health problems with absolute certainty.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: (A) Saos2 cells were transiently cotransfected with pEGFP-N and expression constructs coding for wildtype 53, wildtype HIPK2 or the kinase defective HIPK2 mutant K221A as indicated. After 24 h cells were lysed and analysed by Western blotting with the indicated antibodies. (B) GFP fluorescence was measured by quantitative fluorometry to show equal transfection efficiencies. Background fluorescence was set to 1 (lane 0). Fluorescence fold is increased above background (lanes 1 to 4). Bars, SD. Full size image HIPK2 overexpression does not change Mdm2 mRNA expressionNext we asked the question whether HIPK2 downregulates Mdm2 by decreasing Mdm2 transcription. We transiently transfected Saos2 cells either with vector alone or with expression plasmids coding for p53 or HIPK2. In addition, the plasmid coding for p53 was transiently transfected in the presence of either wildtype HIPK2 or the kinase defective HIPK2 K221A mutant (Fig. 4). Relative Mdm2 mRNA levels were detected by quantitative TaqMan RT-PCR with sequence specific primers for human Mdm2 (GenBank accession AF201370). As expected, p53 led to an approximately 4 fold increase of Mdm2 mRNA levels [16, 17]. In contrast, overexpression of HIPK2 did not lead to a change of Mdm2 mRNA compared to vector transfected controls (Fig. 4). Overexpression of p53 together with either wildtype HIPK2 or the kinase defective HIPK2 mutant K221A showed no significant decrease in p53-induced Mdm2 mRNA levels. Similar data were obtained with HeLa cells (data not shown). Therefore, HIPK2 does not downregulate Mdm2 at the transcriptional level. It seems that HIPK2 destabilizes Mdm2 by modifying the Mdm2 protein. Figure 4Quantitative mRNA Expression levels of Mdm2. Saos2 cells were transiently transfected with the indicated expression constructs. Mdm2 mRNA expression levels were determined by TaqMan RT-PCR as described in Materials and Methods. As internal reference, mRNA expression of GAPDH mRNA was used. [SEP] Justify:

Output: The text provided is unrelated to the claim about urban living and stress levels. It discusses an experimental study on Saos2 cells, targeting the regulation of mRNA levels of Mdm2 by HIPK2 and p53, without mentioning stress, urban living, or any related concepts.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: (2011) Development of sample preparation method for auxin analysis in plants by vacuum microwave-assisted extraction combined with molecularly imprinted clean-up procedure. Chem 399: 3367-3374. (2009) Cadmium toxicity and translocation in rice seedlings are reduced by hydrogen peroxide pretreatment. Regul 59: 51–61. (2021) Effect of Naphthalene acetic acid (NAA) on grain yield and bioeconomic efficiency of coarse rice (Oryza sativa L). Bot 53(6): 1-7. IPPC, 2021. Plant health and climate change. Rome: FAO. Retrieved from (2012) Genetic advances in adapting rice to a rapidly changing climate. J Sci 198(5): 360-73. (2010) Physiological and proteomic approaches to address heat tolerance during anthesis in rice (Oryza sativa L. ). J 61(1):143–156. Janni M, Gullì (2020) Molecular and genetic bases of heat stress responses in crop plants and breeding for increased resilience and productivity. J 71(13): 3780-802. Juliano BO (1971) A simplized assay for milled rice amylase. 6: 334-340. Kurpea J, Smalle JA (2020) Auxin/cytokinin antagonistic control of the shoot/root growth ratio and its relevance for the adaptation to drought and nutrient deficiency stresses. 23:1993. (2022) Impact of cropping pattern and climatic parameters in lower Chenab canal system-a case study from Punjab Pakistan. Agri 12:708. (2019) Concurrent drought and temperature stress in rice: A possible result of the predicted climate change: Effects on yield attributes, eating characteristics, and health promoting compounds. 16(6): 1043. (2005) Auxin response factors ARF6 and ARF8 promote jasomonic acid production and flower maturation. Devlop 132(18): 4107-4118. (2020) Identification of main-effect quantitative trait loci (QTLs) for low-temperature stress tolerance germination- and early seedling vigor-related traits in rice (Oryza sativa L. ). 40(1): 10. -(2020) A GWAS approach to find SNPs associated with salt removal in rice leaf sheath. [SEP] Justify:

Output: The text provides references to multiple studies related to improving crop yield and nutrient content through various interventions. For example, the text mentions the 'Effect of Naphthalene acetic acid (NAA) on grain yield and bioeconomic efficiency of coarse rice,' which suggests that specific plant growth hormone applications can lead to refined improvements in the yield. Additionally, the text discusses genetic advancements and physiological approaches to enhance heat tolerance and adaptation, indicating methodologies that enable precise modifications aimed at improving crop resilience and productivity.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: 2%) with pathogenic/likely pathogenic germline variants in DNA repair genes, excluding MMR genes. 35 Increasing repositories of patients with pan-cancers and paired tumor-normal testing have also allowed the discovery of novel cancer predisposition syndromes, particularly in individuals with multiple primary tumors. 36,37Parallel testing also highlights the need for wider germline genetic testing in cancer types not traditionally associated with hereditary cancer syndromes. A study of tumor-normal sequencing in multiple samples from 88 patients with metastatic neuroendocrine tumors found that 14 patients (16%) had clinically actionable germline variants, suggesting a need for universal germline testing in this rare tumor type. 38 In a study of 15,045 patients who underwent paired testing to determine microsatellite instability (MSI) status, Lynch syndrome was identified in 16. 3% of MSI-high (MSI-H) tumors, 1. 9% of MSI-indeterminate tumors, and 0. 3% of microsatellite stable (MSS) tumors. Among the patients with Lynch syndrome, 50% had tumors other than classic colorectal or endometrial cancers, and 45% of these patients did not meet the clinical criteria for testing. This finding suggests that all patients with MSI-H or MMR-D tumors should undergo genetic evaluation for Lynch syndrome, and highlights the utility of integrating somatic and germline findings. 39 In addition, studies of patients with exocrine pancreatic cancer who underwent parallel tumor-normal genetic testing have found high rates of pathogenic germline alterations ranging from 15. 1% to 19. 8%. 40,41 In fact, genomic alterations in exocrine pancreatic cancers are more likely to be germline than somatic,40 and many are potentially clinically actionable. 42 Accordingly, the recent in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic have recommended germline testing in all patients with pancreatic cancer. 20Limitations of Parallel TestingAlthough these studies are compelling and show that a large proportion of patients may benefit from universal tumor-normal genetic testing, there are limitations and challenges to parallel testing. Many of these studies were conducted at large, tertiary cancer centers and are subject to ascertainment bias, potentially inflating the rates of germline findings. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations and challenges of genetic testing. It highlights that while significant findings have been made in various studies, there are limitations to the predictive capabilities of genetic testing, such as ascertainment bias and the fact that these studies may not fully represent the wider population. This suggests that genetic testing does not provide absolute certainty about future health problems.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Relative Mdm2 mRNA expression is shown and Mdm2 mRNA expression of vector transfected cells was set to 1. Bars, SD. Full size image HIPK2 induces Elk1- but not NFκB-mediated transcriptionTo test the expected influence of HIPK2 on other transcription factors we used a chimeric protein consisting of the GAL4 DNA binding domain fused to the activation domain of the transcription factor Elk1. The transcription activator Elk1 becomes phosphorylated and activated by the MAP (mitogen-activated protein) kinase. Direct or indirect phosphorylation of this transactivator by HIPK2 would activate transcription of the luciferase gene from a reporter plasmid with the GAL4-binding element. Cotransfection of the trans-activator plasmid pFA-Elk1, the luciferase reporter plasmid pFR-Luc and the positive control MEK1 encoding plasmid pFC-MEK1 resulted in an 115 fold increase in luciferase activity in 293 cells compared to pFA2-Elk1 and pFR-Luc transfected control cells (data not shown). In comparison, cotransfection of pFA2-Elk1 and the wildtype HIPK2 expression construct gave only a 6 fold increase (Fig. 5A). This increase was reduced to 3 fold when the kinase defective HIPK2 mutant K221A was used. However, using the carboxy-terminal deletion AC with an intact kinase domain, the increase of luciferase activity was about 17 fold. A possible direct effect of HIPK2 on the luciferase construct has been tested by cotransfection of wildtype HIPK2 and pFR-Luc into 293 cells. In this control, the luciferase activity was similar to the pFR-Luc and pFA2-Elk1 transfected control cells (data not shown). These results suggest that HIPK2 may weakly activate the transactivator Elk1-GAL4 and that the kinase function of HIPK2 is necessary for this activation. The carboxy-terminus of HIPK2 may contain inhibitory sequences for Elk1-phosphorylation. The conclusion is, that HIPK2 seems to activate components of the MAP kinase pathway. The exact role remains to be elucidated. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the influence of HIPK2 on transcription factors and luciferase activity in a cellular context, without mentioning urban living or stress levels. There is no connection to the concept of stress or the impact of urban environments.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: 126(7): 1193–1202. (2012) Tapetal development and abiotic stress: a centre of vulnerability. Biol. 39: 553–559. (2015) Soil application of boron improves the tillering and leaf elongation, panicle fertility, yield and its grain enrichment in fine-grain aromatic rice. J 38(3): 338-354. (2014) Influence of boron nutrition on the rice productivity, kernel quality and biofortification in different system. Res 169: 123-131. (2016) Effect of gibberellic acid on enhancing flowering time in Chrysanthemum morifolium. Bot 48(2): 477-483. (2019) Role of mineral nutrition in alleviation of heat stress in cotton plants grown in glasshouse and field conditions. 9 (1):1–17. (2019) Improved auxin level at panicle initiation stage enhance the heat stress tolerance in rice plants. Conf. 2-4. (2023) Biochar integrated nutrient application improves crop productivity, sustainability and profitability of maize-wheat cropping system. Sustainability 15(3): 2232. (2018) Boron application improves yield of rice cultivars under high temperature stress during vegetative and reproductive stages. Biometeorol 62: 1375–1387. (2018) Auxin protects spikelet fertility and grain yield under drought and heat stresses in rice. Bot 150: 9-24. (2010) Silicon alleviates cadmium toxicity in peanut plants in relation to cadmium distribution and stimulation of antioxidative enzymes. Regul 61:45–52. (2011) High temperature limits in vivo pollen tube growth rates by altering diurnal carbohydrate balance in field-grown gossypium hirsutum pistils. J Plant Physiol. 168:1168–1175. (1980) Lipid peroxidation associated with accelerated aging of soybean axes. 65: 245–248. (2021) Systematic review and meta-analysis of global food security projections to 2050. 1-38. (2014) Alleviation of cadmium toxicity by cerium in rice seedling is related to improved photosynthesis, elevated antioxidant enzymes and decreased oxidative stress. Regul 74: 251-260. úy LT (2022) must narrow down the yield gap to continue a major rice bowl. 3: 217-226. [SEP] Justify:

Output: The text corroborates the claim as it discusses various agricultural studies, including statements like 'Soil application of boron improves the tillering and leaf elongation, panicle fertility, yield and its grain enrichment in fine-grain aromatic rice,' which indicates that specific nutrient modifications lead to improved crop yield. Additionally, it mentions how 'Biochar integrated nutrient application improves crop productivity, sustainability and profitability of maize-wheat cropping system,' supporting the notion of precise modifications for enhancing crop yield and nutrient content.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: In addition, it is unclear whether incidental germline findings in tumor types not traditionally associated with hereditary cancer syndromes are true drivers of disease or are merely passenger mutations. Indeed, especially common tumors such as lung, breast, prostate, and colorectal cancer can occur in individuals with germline mutations in cancer susceptibility genes in a sporadic fashion. Jonsson et al43 examined BRCA1/2 mutations across pan-cancers and found that the role of these mutations in driving cancer phenotypes was dependent on tumor lineage and called into question the utility of clinical decisions based on these mutations. Latham et al39 also found that a small proportion of patients with Lynch syndrome with germline mutations harbored tumors that were MSS and did not exhibit an MMR-D signature, suggesting that the germline mutations may be incidental. However, these studies also highlight the need to obtain both tumor and germline sequencing to fully understand the biology of tumors and separate the true drivers of disease from passenger mutations. Further limiting the universal adoption of parallel testing are difficulties in the interpretation of “normal” tissue when sequencing blood due to clonal hematopoiesis (CH) and mosaicism, which can confound germline results. CH refers to somatic mutations in the hematopoietic lineage that can be identified through the sequencing of blood for normal tissue, and mosaicism refers to differential cell populations with distinct genotypes within one individual. Although genetic variants associated with CH or mosaicism should be present at lower variant fractions than the traditional 50% of germline heterozygous mutations, technical challenges in sequencing and early mosaicism events can make interpretation challenging. 44,45In addition, many centers may not have an existing genetic counseling infrastructure to provide a comprehensive discussion of the risks/benefits of genetic testing and a timely dissemination of sensitive germline results and notification of at-risk relatives. 46 Results from the () study found that electronic genetic education and the release of results without traditional genetic counseling was noninferior with regard to patient distress and was associated with higher test completion rates, suggesting that a paradigm of individualized genetic counseling for patients with positive findings alone may be acceptable. 47 There are also challenges related to informed consent, privacy protection, and future research regarding these germline specimens and data generated through parallel testing. [SEP] Justify:

Output: The text contrasts the claim by highlighting the uncertainties and complications associated with genetic testing. It explains that incidental findings may not be true drivers of disease and that common tumors can arise sporadically even in the presence of genetic mutations. It emphasizes that clinical decisions based on genetic mutations may be questionable and that the interpretation of genetic results is complicated by factors like clonal hematopoiesis and mosaicism. This understanding indicates that genetic testing does not provide absolute certainty regarding future health problems.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Figure 5Activation of Elk 1-mediated transcription but no activation of NFκB by HIPK2 overexpression. (A) 293 cells were cotransfected with a GAL4-luciferase reporter construct, an Elk1-GAL4 transactivator expression construct and the indicated HIPK2 constructs or vector. (B) 293 cells were cotransfected with an NFκB-luciferase reporter construct and the indicated HIPK2 constructs or vector. Results represent the mean of three independent experiments. Bars, SD. Full size image In a similar assay, which we have used to study HIPK2-mediated activation of p53 specific promoter elements, we looked for a role of HIPK2 in activation of NFκB-mediated transcription. 293 cells were cotransfected with a luciferase reporter plasmid containing five tandem NFκB binding sites and different HIPK2 expression constructs (Fig. 5B). Only wildtype HIPK2 activated NFκB-mediated transcription slightly but not significantly. No effect was seen with the HIPK2 mutants (Fig. 5B). NFκB-mediated luciferase activation was 100 fold with a MEK kinase positive control plasmid (data not shown). The luciferase values of vector and pNF-κB-luc transfected cells were set as 1. Taken together, we conclude that HIPK2 does not activate NFκB. DiscussionHIPK2 enhances p53 activity and p53 expression or stabilityHIPK2 acts as a co-repressor for homeodomain containing transcription factors. We show here that HIPK2 has additional functions, namely the activation of transcription mediated by p53 specific promoter elements. Thereby, overexpression of HIPK2 leads to an increase of the p53 protein level. Neither the transcriptional activation nor the enhancement of p53 protein amounts is detected with overexpressed HIPK2 mutants. The p53 responsive enhancer element becomes activated by HIPK2 in cell lines with p53 but not in a cell line devoid of p53 (Fig. 1). We conclude, that the activation of the enhancer element is indeed mediated by p53 and not by another transcription factor of the p53 family. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the activation of transcription factors in cells and the role of HIPK2, without mentioning urban living, stress levels, or any related topics.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: Skip to Content eLife home page your research Search by keyword or author Reset form my search to 10. 7554/eLife. 84988 Open access Copyright information Version of RecordAugust 1, 2023 Open annotations (there are currently 0 annotations on this page). 1,727 views 420 downloads 21 4988. Copy to clipboard Download BibTeX Download. RIS Full text Figures and data Peer review Side by side Abstract Editor's evaluation and methods Data availability 10. 7554/eLife. 84988. sa0 Decision letter Reviews on Sciety eLife's review process alter the soil they live in, and thereby modulate the growth and defense status of other plants (Bever et al. , 1997). These so-called plant-soil feedbacks can influence plant community composition and ecosystem functions (Bennett et al. , 2017; Teste et al. , 2017; Mariotte et al. , 2018). They have also been used for centuries in crop rotation schemes to reduce pest, weed and disease pressure and ultimately improve crop yields (White, 1970; van der Putten et al. , 2013). So far, however, proximate mechanistic work on plant-soil feedbacks has rarely been applied to improve crop rotations. Thus, the benefits of this research for the engineering of crop rotations for ecological and sustainable agriculture remain limited (Mariotte et al. , 2018). Plant-soil feedbacks can act on a variety of plant traits. Reductions in germination through allelochemicals for instance are common and can be attributed to either direct toxicity or delayed germination resulting from biochemical recognition by the seeds (Tawaha and Turk, 2003; Renne et al. , 2014). Changes in defense expression leading to differences in herbivore performance and preference (Pineda et al. , 2010; Kos et al. , 2015; Hu et al. , 2018b; Pineda et al. , 2020) and alterations in susceptibility to soil pathogens have also been observed (Ma et al. , 2017). Finally, changes in hormonal balance have been linked to effects on plant growth and biomass accumulation (Pieterse et al. , 2014; Hu et al. , 2018a). The response to plant-soil feedbacks can strongly depend on environmental conditions (Smith‐Ramesh et al. [SEP] Justify:

Output: The text corroborates the claim by discussing how plant-soil feedbacks, which can be modified, influence plant community composition and ecosystem functions. It states that these interactions have been used historically in crop rotation schemes to reduce pest and disease pressure, thus improving crop yields. This supports the claim that precise modifications, through understanding plant-soil interactions, can enhance agricultural productivity.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: 48,49 Given these challenges, working groups have been formed to discuss best practices for the integration of somatic and germline data to facilitate the interpretation and application of data. 24to ImplicationsDespite these limitations and challenges, the necessity of parallel tumor-normal testing is becoming more apparent as the actionability of germline findings expands with an increasing number of FDA-approved therapeutics with germline indications (Table 2). Early studies of targeted therapies for germline indications were conducted in basal cell carcinomas50 and thyroid cancers. 51 Both studies included a significant number of patients with known genetic cancer predisposition syndromes—Gorlin syndrome and multiple endocrine neoplasia 2 syndrome—and found efficacy in those populations. Recently, another RET inhibitor, selpercatinib, was approved for RET-mutant medullary thyroid cancers. 52 Targeted therapies, including everolimus and selumetinib, have also been studied in rare, genetic conditions associated with multiple cancer types, such as tuberous sclerosis and neurofibromatosis 1. 53–55Table 2. Selected FDA Approvals for a study of the PD-1 inhibitor pembrolizumab in patients with advanced/metastatic solid tumors with MMR-D who experienced disease progression on traditional chemotherapy found efficacy in this population. The study included many patients with Lynch syndrome with tumors exhibiting MMR-D, the hallmark of Lynch syndrome–associated cancers. 56 As a result, pembrolizumab received the first tumor-agnostic indication from the FDA for all MMR-D/MSI-H tumors, including those in patients with Lynch syndrome. More recently, PARP inhibitors have gained multiple germline-based FDA approvals in a variety of tumor types. In women with ovarian cancer and germline BRCA mutations, the PARP inhibitor olaparib was shown to be effective as a treatment in the recurrent setting and as maintenance in the up-front setting. 57,58 Subsequently, multiple PARP inhibitors have been approved in ovarian cancer for a wider population of women, including those with somatic BRCA mutations,59 those with homologous repair–deficient (HRD) tumors,60,61 and in all patients as maintenance therapy. 62 PARP inhibitors are also approved in metastatic breast cancer for patients with germline BRCA1/2 mutations. [SEP] Justify:

Output: The text contrasts the claim by highlighting the limitations and challenges of genetic testing. It discusses the necessity of integrating data from both somatic and germline sources due to these challenges and mentions that while there are FDA-approved therapeutics based on genetic findings, it does not imply that genetic testing can predict all future health problems with absolute certainty.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: The kinase defective mutant of HIPK2, K221A, leads to a decrease of p53 protein amounts (Fig 2A). However, this decrease does not correspond with a further decrease on p53-mediated transcription compared to HIPK2 mutants AC and AN (Fig. 1A and 1B). HIPK2 is not sufficient for phosphorylation of crucial serine residues of p53The nuclear phosphoprotein p53 is regulated and stabilized by different modifications [3, 18], e. g. serine 15 phosphorylation has been detected as prerequisite for phosphorylation of tyrosine residue 18 [19]. HIPK2 could not activate or stabilize p53 either directly or indirectly by phosphorylation. DNA damaging agents such as doxorubicin induce increased p53 phosphorylation by as yet undefined mechanisms. In the presence of wildtype HIPK2 and doxorubicin, serine residue 15 and 20 of p53 become phosphorylated, which could be either due to transfected or endogenous HIPK2 of HeLa cells. In the presence of doxorubicin alone or together with mutants of HIPK2 serines 15 and 20 could be phosphorylated by endogenous HIPK2 (Fig. 2C). Thus, we conclude that HIPK2 is not sufficient for serine 15 and 20 phosphorylation, for which doxorubicin may be required. HIPK2 is also not sufficient for phosphorylation of residue 392, but doxorubicin requirement is excluded. Additional phosphorylation sites have not been tested since the absolute requirement of phosphorylation for DNA-damage induced stabilization of p53 remains controversial [20]. Other proteins, which regulate p53, like e. g. Mdm2, could be the targets for phosphorylation by HIPK2. Doxorubicin treatment and HIPK2 overexpression show an additive effect on p53 protein expression or stability (Fig. 2B). The relative amounts of the increase of the p53 protein levels and the increase in doxorubicin induced phosphorylation of serine residue 15 are comparable and give rise to the assumption that the total amount of p53 protein present becomes phosphorylated under doxorubicin treatment. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the regulation and phosphorylation of the p53 protein in the context of HIPK2 and doxorubicin treatment, without any reference to urban living or stress levels. It focuses on molecular biology and does not address the relationship between urban living and stress.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: Benzoxazinoids are a class of indole-derived secondary metabolites that are produced and released in high quantities by important food crops such as maize and wheat (Frey et al. , 2009; Hu et al. , 2018b). Multiple functions of benzoxazinoids have been described, ranging from defense to nutrient uptake (Niemeyer, 2009). Soil conditioning by benzoxazinoids can feed back on growth and defense of maize and wheat, where the strength and direction of the feedback depend on the plant genotype and soil characteristics (Hu et al. , 2018b; Cadot et al. , 2021a). Benzoxazinoids can shape root microbial communities (Hu et al. , 2018b; Cotton et al. , 2019; Kudjordjie et al. , 2019; Cadot et al. , 2021b), chelate iron in the soil and possibly reduce the performance of non-benzoxazinoid producing plants via allelopathic effects (Bigler et al. , 1996; Niemeyer, 2009; Hu et al. , 2018a). Thus, they may influence crop rotations and yields through a variety of plant-soil feedback mechanisms. To test whether benzoxazinoids can influence crop yields in a rotation scheme, we investigated how maize benzoxazinoids affect weed and pest pressure, germination, growth, yield, and food quality of wheat plants in the field. Maize and wheat are among the most important crops in global food production and are commonly cultivated in sequence in rotation schemes. In a 2-year field experiment involving wild type and benzoxazinoid-deficient bx1 mutant maize plants, we first evaluated the effects of benzoxazinoid soil conditioning on soil chemistry and microbial communities. In the following season, we planted three wheat varieties into the same field and quantified a wide variety of agronomically important traits, including growth, weed cover, insect damage, yield and yield quality. Through this experiment, we demonstrate that root exudation of secondary metabolites can be linked directly to improved food production under an agronomically realistic crop rotation scenario. [SEP] Justify:

Output: The text corroborates the claim by demonstrating that benzoxazinoids, derived from maize, can influence crop yields through various mechanisms such as soil conditioning and root exudation of secondary metabolites. It emphasizes the connection between these metabolites and improved food production under rotation schemes, which directly relates to improving crop yield and nutrient content.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: 63,64 Interestingly, in metastatic prostate cancer, rucaparib is approved for patients with BRCA1/2 mutations33,65; however, olaparib is approved in those with a wider range of germline HRD genes. 66,67 Olaparib was also recently approved in patients with metastatic pancreatic cancer and germline BRCA1/2 mutations. 42 These studies suggest that knowledge of germline mutations, particularly those in BRCA1/2 or other HRD genes, may influence the effectiveness of PARP inhibitors and affect clinical management. Future of Parallel Testing: DecisionsAs the number of germline indications for therapies—both FDA-approved and for clinical trials—increases, germline results from parallel tumor-normal testing are directly impacting treatment decisions. 68 In a study of 11,947 patients who underwent parallel tumor-normal testing with 1,042 (9%) had a likely pathogenic/pathogenic germline alteration in a gene with a targeted therapy that was FDA-approved or had supporting data of such quality that it might warrant future approval. Most mutations were in BRCA1/2, ATM, or Lynch genes, and the most common cancer types represented were ovarian, breast, pancreatic, and prostate cancers. Notably, among the subset of patients with advanced cancer, 40% received germline-directed treatment. Common targeted therapies included PARP and checkpoint inhibitors. 69 These studies highlight the importance of parallel testing in expanding the population of patients receiving germline genetic information to not only improve the assessment of inherited risk but also expand therapeutic options. Testing to Types? Given the increasing therapeutic implications of germline findings, there have been major updates to recommendations for genetic testing in various cancer types. 70 Although universal germline testing for BRCA mutations had been recommended for ovarian cancer, this recommendation has now expanded to patients with metastatic breast cancer, metastatic prostate cancer, and pancreatic cancer. In addition, there are expanded recommendations for MMR staining and MSI testing in all patients with colorectal and endometrial cancer. As germline testing expands across tumor types, there is a question of whether patients with earlier-stage, nonmetastatic cancers should undergo germline testing because targeted therapies are moving into earlier stages of disease. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations and specific applications of genetic testing. It emphasizes that while genetic testing can provide valuable information about germline mutations and influence treatment decisions, it does not guarantee predictions for all future health problems with absolute certainty. For example, it highlights that genetic testing results impact treatment choices rather than predicting all health conditions.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Since p53 has a high turnover rate [4], the increase of p53 protein levels seems to be due to stabilization of p53 rather than induction of enhancement of transcription of p53. An increase of p53 mRNA stability or translation efficiency could play additional roles. HIPK2 downregulates Mdm2 proteinHIPK2 may exert all its effects on p53 via Mdm2, since it leads to a decrease of the p53-induced Mdm2 protein level (Fig. 3). HIPK2 has no influence on Mdm2 transcription (Fig. 4). Therefore, HIPK2 regulates Mdm2 stability at the protein level. The most likely mechanism is serine/threonine phosphorylation of Mdm2 either directly or indirectly by HIPK2. At present, we did not get convincing data showing a direct serine/threonine phosphorylation of Mdm2 by HIPK2. Mdm2 shuttles between the nucleus and the cytoplasm and this nucleo-cytoplasmic shuttling of Mdm2 is essential for its ability to promote p53 degradation by the cytoplasmic proteasome [21]. Mdm2 seems to have a role in exporting p53 from the nucleus [22, 23]. HIPK2 did not directly interact with either p53 or Mdm2 in yeast and 293T cells (data not shown). Whether HIPK2 can influence the shuttling of Mdm2 remains to be clarified. Effect of HIPK2 on target genes of p53We have addressed the issue to check expression of described downstream targets of p53 at the protein level in HeLa cells. The best characterized target gene that becomes transactivated by p53 is the cyclin/Cdk inhibitor p21 (Waf1/Cip1) [3]. But we did not detect a significant increase of expression of p21 (Waf1/Cip1) mediated by overexpression of HIPK2 or treatment with doxorubicin in Western blotting analysis. As a positive control 2 μg of the wildtype p53 expression construct pFC-p53 was transiently transfected and transient overexpression of wildtype p53 led to a weak increase of p21 (Waf1/Cip1) expression (data not shown). [SEP] Justify:

Output: The text is irrelevant to the claim because it discusses biochemical mechanisms related to p53 and HIPK2 without mentioning urban living or stress levels. There is no connection to the assertion that urban living leads to increased stress.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: Benzoxazinoid soil conditioning improves wheat emergence and growth To investigate whether benzoxazinoid soil conditioning affects wheat performance, we measured emergence shortly after sowing as well as leaf chlorophyll content, plant height and aboveground biomass during wheat growth of the three varieties. Overall, wheat seedling emergence was increased by 8% in benzoxazinoid conditioned soils (Figure 3A). Chlorophyll content measured in the youngest fully developed leaf (as a proxy for early plant performance) was also increased in plants growing in benzoxazinoid conditioned soils (Figure 3B). Wheat growth, height, and biomass production per area, as well as shoot water content were also enhanced (Figure 3C/D, Figure 3—figure supplement 1). Thus, benzoxazinoid soil conditioning increases wheat performance across different wheat varieties. Figure 3 with 1 supplement see all Download asset Open asset Benzoxazinoid soil conditioning improves wheat emergence and growth. (A) Seedling emergence, (B) chlorophyll content, (C) plant height, and (D) shoot dry weight of three wheat varieties sown in soils previously conditioned with wild type (WT) or benzoxazinoid-deficient bx1 mutant maize. Means ±SE, boxplots, and individual datapoints are shown (n=20). ANOVA tables and pairwise comparisons within each wheat variety (FDR-corrected p values) are included. Cond: soil conditioning (WT or bx1). Var: wheat variety. ‘C x V’: interaction between conditioning and wheat variety. Note that the minimum values of the y-axes were set to a value greater than zero for clearer visualization of treatment differences. Figure 3—source data 1 Data of phenotypes shown in Figure 3 and Figure 3—figure supplement 1. Download elife-84988-fig3-data1-v1. xlsx Benzoxazinoid soil conditioning does not change weed pressure, but reduces insect infestation To test for possible changes in weed pressure due to allelopathic effects, we surveyed the weed cover on all plots. Chickweed (Stellaria media), Persian speedwell (Veronica persica), and Shepherd’s purse (Capsella bursa-pastoris) were the most abundant weeds. [SEP] Justify:

Output: The text corroborates the claim by providing evidence that benzoxazinoid soil conditioning leads to significant improvements in various aspects of wheat performance, such as increased seedling emergence, higher chlorophyll content, enhanced plant height, and aboveground biomass. These enhancements indicate precise modifications that allow for improved crop yield and nutrient content.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: For example, there are ongoing adjuvant studies of checkpoint inhibitors in patients with Lynch syndrome with endometrial cancer (GY020; ClinicalTrials. gov identifier: NCT04214067) and colon cancer (NCT02912559) and adjuvant studies of PARPi in women with breast cancer and germline BRCA mutations (OlympiA; NCT02032823). Preliminary data also support the efficacy of PARPi monotherapy as neoadjuvant treatment in women with germline BRCA mutations and operable breast cancer,71 with an ongoing phase III trial (NCT03499353). Call to Action: in With CancerThe integration of somatic and germline testing is critical to comprehensively characterize pathogenic germline mutations, accurately assess drivers of cancer risk, and make therapeutic decisions. Going forward, there may be a benefit to parallel next-generation sequencing tumor-normal testing for all patients with cancer. In addition, studies show that patients are very interested in paired testing and in obtaining germline results. 72 As parallel testing becomes more common, there will be a need to carefully interpret results for both therapeutic potential and cancer predisposition risk. Challenges for moving forward include decisions on multigene, tumor-agnostic germline panels versus more disease-directed panels, and the need for innovative systems to provide the appropriate counseling and dissemination of results. However, expanded germline testing may continue to have unforeseen benefits, such as expanded opportunities for cascade testing,73 potentially benefiting not only patients but also their at-risk relatives. 1. ↑Offit K. Decade in review—genomics: a decade of discovery in cancer genomics. 2014;11:632–634. CrossrefPubMedOffit K. Decade in review—genomics: a decade of discovery in cancer genomics. 2014;11:632–634. 10. 1038/nrclinonc. 2014. 17025286975)| falseSearch 2. ↑ of policy statement update: genetic and genomic testing for cancer susceptibility. J 2015;33:3660–3667. of policy statement update: genetic and genomic testing for cancer susceptibility. J 2015;33:3660–3667. 10. 1200/JCO. 2015. 63. 0996)| falseSearch 3. ↑ Cancer genomics and inherited risk. J 2014;32:687–698. genomics and inherited risk. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations and complexities of genetic testing for cancer and health predispositions. It highlights that while genetic testing ('germline testing') is critical for assessing cancer risk and therapeutic decisions, it does not guarantee absolute predictions of future health problems. Specifically, it notes the need for careful interpretation of results and that challenges exist in the decision-making process regarding the type of genetic tests (multigene vs. disease-directed). This implies that genetic testing cannot predict all future health problems with absolute certainty.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Western blotting does not seem to be sensitive enough to detect a significant difference in p21 expression between vector and wildtype HIPK2 transfected cells. In the same experimental setting an increase of expression of the pro-apoptotic Bcl2 family member Bax, whose gene has been described as a p53 target [3], was not detectable (data not shown). Therefore, induction of p53 target genes seems to be cell type specific. The recently described p53-dependent pro-apoptotic Bcl-2 family member Noxa [24] is a further candidate that could be regulated via HIPK2. In this respect, a further difficulty is that HIPK2 downregulates the p53-induced Mdm2 protein level. This may also be the case for other p53-induced proteins. Other functions of HIPK2HIPK2 is also termed PKM (for Mx-interacting protein kinase) since it has been cloned in a yeast two-hybrid screen as an interaction partner for the interferon type I-induced protein MxA, that displays antiviral activity against a variety of RNA viruses [10]. The nuclear distribution of murine Mx1 is similar to HIPK2/PKM, but a direct interaction of the Mx protein with HIPK2/PKM and phosphorylation of Mx by HIPK2/PKM could not be demonstrated so far [10]. HIPK2/PKM phosphorylates several phosphoproteins expressed in E. coli. This reaction is inhibited by a kinase defective mutant K221W of HIPK2/PKM. Thereby it was also shown that HIPK2/PKM is a true serine/threonine kinase, rather then a dual specificity protein kinase which is able to phosphorylate both, serine/threonine and tyrosine residues [10]. HIPK2 interacts with the death factor receptor CD95 in the yeast two-hybrid system [25]. When overexpressed in mammalian cells it associates with TRADD [26]. TRADD has been described to bind to the tumor necrosis factor type I and thereby executing essential functions in signaling [27, 28]. Whether HIPK2 plays an important role in death receptor mediated apoptosis is not clear at present. [SEP] Justify:

Output: The text is irrelevant to the claim, as it discusses scientific findings related to the protein HIPK2 and its role in apoptosis without addressing any topics related to urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: No significant influence of benzoxazinoid soil conditioning was found (Figure 4—figure supplement 1). Benzoxazinoid soil conditioning increases wheat biomass and yield without compromising grain quality To understand how benzoxazinoid soil conditioning influences mature wheat plants, we also quantified plant performance at harvest. All wheat varieties had a higher number of tillers per area in benzoxazinoid conditioned soils (Figure 5A). To test if these differences can be attributed to differences in emergence or differences in tillering, we also counted the number of tillers per plant. Overall, plants in benzoxazinoid conditioned soils produced a higher numbers of tillers per plant. This pattern was consistent across all varieties, with the most pronounced difference in the variety Sailor (Figure 5B). Next, we measured if the higher tiller density resulted in a higher aboveground biomass per area. Consistent with the results during wheat growth, benzoxazinoid soil conditioning also increased biomass at plant maturity (Figure 5C). The weight of individual tillers was similar (Figure 5D), demonstrating that benzoxazinoid soil conditioning increased biomass by promoting tiller density, both through enhanced germination and tillering, rather than tiller weight. Figure 5 Download asset Open asset Benzoxazinoid soil conditioning increases wheat density and biomass. (A) Tiller density, (B) reproductive tillers per plant, (C) shoot dry weight, and (D) dry weight per tiller of the three wheat varieties growing in soils previously conditioned with wild type (WT) or benzoxazinoid-deficient bx1 mutant maize. Means ±SE, boxplots, and individual datapoints (n=20) are shown. ANOVA tables and pairwise comparisons within each wheat variety (FDR-corrected p values) are included. Cond: soil conditioning (WT or bx1). Var: wheat variety. ‘C x V’: interaction between conditioning and wheat variety. Pos: position on the field. Note that the minimum values of the y-axes were set to a value greater than zero for clearer visualization of treatment differences. Figure 5—source data 1 Data of phenotypes shown in Figure 5. Download elife-84988-fig5-data1-v1. xlsx We evaluated whether benzoxazinoid soil conditioning improved wheat yield and quantified kernel weight per plot at harvest. [SEP] Justify:

Output: The text corroborates the claim by providing evidence that benzoxazinoid soil conditioning increases wheat biomass and yield. It describes how this soil conditioning leads to a higher number of tillers per area and enhances biomass without compromising grain quality. Furthermore, it indicates that the increased tiller density contributes to the higher yield and overall plant performance, supporting the notion that such modifications can improve crop yield significantly.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: J 2014;32:687–698. 2444924410. 1200/JCO. 2013. 49. 7271)| falseSearch 4. ↑Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J 2007;25:1329–1333. . Meta-analysis of BRCA1 and BRCA2 penetrance. J 2007;25:1329–1333. 1741685310. 1200/JCO. 2006. 09. 1066)| falseSearch 5. ↑Samadder NJ, Riegert-Johnson D, Boardman L, et al. Comparison of universal genetic testing vs guideline-directed targeted testing for patients with hereditary cancer syndrome. JAMA Oncol 2021;7:230–237. -Johnson D, Boardman L, Comparison of universal genetic testing vs guideline-directed targeted testing for patients with hereditary cancer syndrome. JAMA Oncol 2021;7:230–237. 3312624210. 1001/jamaoncol. 2020. 6252)| falseSearch 6. ↑ Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. 2017;23:703–713. landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. 2017;23:703–713. 2848135910. 1038/nm. 4333)| falseSearch 7. ↑Collins FS, Varmus H. A new initiative on precision medicine. N Med 2015;372:793–795. . A new initiative on precision medicine. N Med 2015;372:793–795. 10. 1056/NEJMp150052325635347)| falseSearch 8. ↑. Implementing genome-driven oncology. Cell 2017;168:584–599. . Implementing genome-driven oncology. Cell 2017;168:584–599. 2818728210. 1016/j. cell. 2016. 12. 015)| falseSearch 9. ↑ Molecular landscape and actionable alterations in a genomically guided cancer clinical trial: Analysis for (NCI-MATCH). J 2020;38:3883–3894. landscape and actionable alterations in a genomically guided cancer clinical trial: Analysis for (NCI-MATCH). J 2020;38:3883–3894. 10. 1200/JCO. [SEP] Justify:

Output: The text contrasts the claim by discussing various studies and analyses related to genetic testing for hereditary cancer syndromes and the penetrance of BRCA1 and BRCA2 genes. These references imply that while genetic testing provides valuable information, it does not guarantee absolute certainty in predicting all future health problems, suggesting limitations in the predictive capabilities of genetic testing.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Recently, it has been described that HIPK3, a member of the HIPK family, binds to CD95 and thereby inhibits c-Jun N-terminal kinase activation [29]. An additional function of HIPK2 may be the activation of the mitogen-activated protein kinase pathways since we detected a weak activation of Elk1 mediated transcription. The carboxy-terminal deletion of HIPK2 ΔC augments the activation of Elk1-mediated transcription in comparison to wildtype HIPK2. The carboxy-terminal deletion of HIPK2 ΔC is equally distributed in the nucleus. In contrast, wildtype HIPK2 and the kinase defective K221A mutant localize to nuclear speckles [25]. This suggests that the equal nuclear distribution of the HIPK2 mutant ΔC is responsible for the increase in Elk1 mediated transcription. It has been shown that DNA damage in addition to stabilization of p53 leads to an activation of a MAP kinase homolog, the c-Jun N-terminal kinase or stress activated protein kinase [30]. ConclusionsHIPK2 is a nuclear kinase that activates transcription mediated by tumor suppressor p53 responsive promoter elements upon overexpression. Furthermore, it plays a role in the induction of expression or stability of p53 protein. Overexpression of HIPK2 does not lead to a change of Mdm2 mRNA levels, but it leads to a downregulation of p53-induced Mdm2 protein. Most likely, this HIPK2-induced decrease of Mdm2 is responsible for the stabilization of p53. The involvement of HIPK2 kinase activity remains to be identified. Materials and methodsCell lines and cell cultureHeLa cells were maintained in RPMI 1640 containing 10% heat-inactivated fetal bovine serum, L-glutamine, and penicillin/streptomycin (all from Technologies, Karlsruhe, Germany). The stock solution of doxorubicin (Amersham-Pharmacia, Freiburg, Germany) was 2 mg/ml in H20. [SEP] Justify:

Output: The text is irrelevant to the claim about urban living and stress levels. It discusses the molecular mechanisms of HIPK2 and its interactions in cellular contexts, but does not mention urban living, stress, or any related psychological or sociological impacts.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: For each Claro and Fiorina plot, 9 m2 were harvested. Final yield could not be determined for Sailor, as this field was harvested in bulk for seed multiplication. Yield in both Claro and Fiorina was increased by 4–5% on benzoxazinoid conditioned soils (Figure 6A); the productivity of both varieties fell within the expected range of top-yielding winter wheat varieties in Switzerland (variety testing Agroscope). The number of kernels per tiller, the kernel weight per tiller and the thousand kernel weight did not differ between soil conditioning treatments (Figure 6B, Figure 6—figure supplement 1A, B), showing that the increase in yield is primarily the result of more kernels being produced per area. Figure 6 with 2 supplements see all Download asset Open asset Benzoxazinoid soil conditioning increases wheat yield without compromising grain quality. (A) Yield of two wheat varieties growing in soils previously conditioned with wild type (WT) or benzoxazinoid-deficient bx1 mutant maize. Kernel quality measures included (B) thousand kernel weight, (C) kernel protein content, (D) Zeleny index (flour quality), (E) dough stability, and (F) PCA of kernel micronutrient composition. For (A–E) means ±SE, boxplots, and individual datapoints are shown (n=10). ANOVA tables and pairwise comparisons within each wheat variety (FDR-corrected p values) are included. (F) reports the first two axes of the micronutrient PCA, including individual samples and the contribution of the 10 elements explaining most of the variation in the dataset (arrow length denotes relative contribution). Cond: soil conditioning (WT or bx1). Var: wheat variety. ‘C x V’: interaction between conditioning and wheat variety. Pos: position on the field. Note that the minimum values of the y-axes were set to a value greater than zero for clearer visualization of treatment differences. Figure 6—source data 1 Data of phenotypes shown in Figure 6, Figure 6—figure supplement 1 and Figure 6—figure supplement 2. Download elife-84988-fig6-data1-v1. xlsx To investigate whether the increased wheat yield comes with a penalty in terms of grain quality, we first determined a number of physical kernel properties. [SEP] Justify:

Output: The text corroborates the claim by demonstrating that soil conditioning with benzoxazinoids resulted in a 4-5% increase in yield for two wheat varieties. It discusses how the yield increase is attributed to the production of more kernels per area, aligning with the idea of making precise modifications to enhance crop yield. Additionally, the text mentions efforts to assess grain quality, which relates to nutrient content.


Input: Task: contrast the claim using the given text. Claim: Genetic testing can predict all future health problems with absolute certainty. [SEP] Text: 19. 03010)| falseSearch 10. ↑Mandelker D, Ceyhan-Birsoy O. Evolving significance of tumor-normal sequencing in cancer care. 2020;6:31–39. -Birsoy O. Evolving significance of tumor-normal sequencing in cancer care. 2020;6:31–39. 10. 1016/j. trecan. 2019. 11. 00631952779)| falseSearch 11. ↑Trottier AM, Cavalcante de M, Li Z, et al. Somatic mutation panels: time to clear their names. 2019;235:84–92. de mutation panels: time to clear their names. 2019;235:84–92. 10. 1016/j. cancergen. 2019. 04. 06531101556)| falseSearch 12. ↑Mandelker D. Toward concurrent testing for somatic and germline variants in cancer patients. Res 2016;22:3987–3988. CrossrefPubMedMandelker D. Toward concurrent testing for somatic and germline variants in cancer patients. Res 2016;22:3987–3988. 10. 1158/1078-0432. CCR-16-104327307597)| falseSearch 13. ↑Mandelker D, Zhang L. The emerging significance of secondary germline testing in cancer genomics. J Pathol 2018;244:610–615. . The emerging significance of secondary germline testing in cancer genomics. J Pathol 2018;244:610–615. 10. 1002/path. 503129293272)| falseSearch 14. ↑. The role of genetic counseling in familial and sporadic cancer: considerations, challenges, and collaboration. Med 2017;167:884–885. . The role of genetic counseling in familial and sporadic cancer: considerations, challenges, and collaboration. Med 2017;167:884–885. 10. 7326/M17-251229086794)| falseSearch 15. ↑ of policy statement update: genetic and genomic testing for cancer susceptibility. J 2010;28:893–901. of policy statement update: genetic and genomic testing for cancer susceptibility. J 2010;28:893–901. 10. 1200/JCO. 2009. 27. 0660)| falseSearch 16. ↑ A computational approach to distinguish somatic vs. [SEP] Justify:

Output: The text discusses the evolving significance of tumor-normal sequencing and the role of genetic counseling in genetic testing, but does not assert that genetic testing can predict all future health problems with absolute certainty. This implies limitations in the predictive power of genetic testing, contrasting with the claim.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Human osteosarcoma Saos2 cells and human embryonic kidney 293 cells were cultured in Dulbecco's modified Eagle's medium containing 10% heat-inactivated fetal bovine serum, L-glutamine, and penicillin/streptomycin (all from Technologies, Karlsruhe, Germany). Plasmids, construction of expression plasmids, mutagenesis and transient transfectionThe full length human HIPK2 cDNA [25] was subcloned into the EcoR1 and XhoI sites of pcDNA3. 1-zeo(+) (Invitrogen, Groningen, The Netherlands). The DNA fragments for the deletion constructs were generated by PCR using polymerase (Biolabs, Frankfurt, Germany) and primers with appropriate restriction sites and epitope tags. Details about the used primers can be obtained upon request. The carboxy-terminal HIPK2 deletion AC contains amino acids until position 527, the amino-terminal deletion AN from amino acid position 559. The PCR fragments were subcloned in pBSIIsk(-) (Stratagene, Offenbach, Germany), sequenced using an automated sequencer (Applied Biosystem, Langen, Germany) and inserted into pcDNA3 (Invitrogen, Groningen, The Netherlands). The point mutant HIPK2 K221A was generated using the QuickChangeTM kit (Stratagene, Offenbach, Germany) according to the manufacturer's instructions. The plasmid pEGFP-Nl coding for a green fluorescent protein was obtained from Clontech (Heidelberg, Germany). The plasmid coding for wildtype p53 was a kind gift from M. Oren (Institute of Science, Israel). HeLa and Saos2 cells were transiently transfected by using the () according to the protocol of the manufacturer. Transient transfections of 293 cells were performed by the calcium phosphate method. Prior to transfection approximately 5 × 105 cells were plated onto a 60 mm dishes to a confluency of 20%. Cells were harvested at 20–30 h following transfection and lysed in 500 μl of lysis buffer (20 mpH 7. 4, 150 mM NaCl, 5 mM EDTA, 10 % glycerol, 0. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the methodology for culturing cells and plasmid construction, without mentioning urban living, stress levels, or any related concepts. Therefore, it does not support, contrast, or pertain to the claim regarding urban living and stress.


Input: Task: corroborate the claim using the given text. Claim: It allows for precise modifications to improve crop yield and nutrient content. [SEP] Text: Volume per weight, kernel surface area, kernel length and kernel width were not affected by soil conditioning (Figure 6—figure supplement 1C–F). We further assessed various agronomically important parameters that are indicative of kernel quality and suitability for baking. We measured protein content, Zeleny index, falling number, as well as dough water absorption, stability and softening. Kernel quality and baking quality were high and showed no differences between soil conditioning treatments (Figure 6C–E, Figure 6—figure supplement 1G–I). To test if micronutrient content is affected by soil conditioning, we also quantified 21 elements in the harvested wheat kernels. No benzoxazinoid conditioning effects were found (Figure 6F, Figure 6—figure supplement 2). Taken together, these results demonstrate that maize benzoxazinoid soil conditioning increases wheat yield without affecting kernel quality. exude secondary metabolites into the rhizosphere and thereby influence the growth and defense of subsequently growing plants (Hu et al. , 2018b; Cadot et al. , 2021a). Whether this phenomenon is also relevant in the field, and whether it can be exploited to improve crop productivity, is unknown. Here, we demonstrate that maize plants releasing benzoxazinoids can improve plant growth and crop yield via plant-soil feedbacks under agronomically realistic conditions. Below, we discuss the mechanisms underlying this phenomenon as well as its potential to improve sustainable food production. Translating plant-soil feedback mechanisms to crop resistance and productivity has been proposed as a promising approach in sustainable agriculture (Mariotte et al. , 2018). Plant secondary metabolites and their degradation products are known to suppress the growth of other plants (Schandry and Becker, 2020) and improve herbivore and pathogen resistance (Niemeyer, 2009). Less is known about their potential to influence seedling establishment (Lamichhane et al. , 2018), yield quantity and yield quality in the field (Cadot et al. , 2021a; Pang et al. , 2021). We found that benzoxazinoid soil conditioning by the preceding crop increased subsequent wheat emergence, tillering and plant performance in the field, resulting in higher plant biomass and kernel yield. [SEP] Justify:

Output: The text corroborates the claim by providing evidence that maize benzoxazinoid soil conditioning can lead to increased wheat emergence, tillering, and overall plant performance, resulting in higher biomass and kernel yield. This suggests that the modifications through soil conditioning indeed contribute to improved crop yield, aligning with the claim's assertion.