scholarly journals Molecular response of Sargassum vulgare to acidification at volcanic CO2 vents: insights from de novo transcriptomic analysis

2017 ◽  
Vol 26 (8) ◽  
pp. 2276-2290 ◽  
Author(s):  
Amit Kumar ◽  
Immacolata Castellano ◽  
Francesco Paolo Patti ◽  
Massimo Delledonne ◽  
Hamada Abdelgawad ◽  
...  
2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Aya Nakaya ◽  
Shinya Fujita ◽  
Atsushi Satake ◽  
Takahisa Nakanishi ◽  
Yoshiko Azuma ◽  
...  

Dasatinib is currently approved for clinical use as a first-line treatment agent for newly diagnosed chronic myeloid leukemia (CML). However, only a few clinical trials have been performed to evaluate dasatinibinduced PE following first-line therapy. We investigated the incidence and clinical features of dasatinib-induced PE following first-line therapy in Japanese CML patients of real world clinical practice settings. Among 22 patients, the median age of PEpositive patients was higher than that of PEnegative patients. Major molecular response was achieved in 75% of PE-positive patients and 50% of PE-negative patients. Most patients developed PE more than 1 year after treatment. Appearance of PE is associated with better clinical response during dasatinib treatment, however it is developed at any time. Elderly and high-risk patients tend to develop PE. The clinical features of dasatinib-induced PE following first-line therapy might be late onset and might not immediately follow the increasing of large granular lymphocyte.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8088 ◽  
Author(s):  
Marcelo González-Aravena ◽  
Nathan J. Kenny ◽  
Magdalena Osorio ◽  
Alejandro Font ◽  
Ana Riesgo ◽  
...  

Although the cellular and molecular responses to exposure to relatively high temperatures (acute thermal stress or heat shock) have been studied previously, only sparse empirical evidence of how it affects cold-water species is available. As climate change becomes more pronounced in areas such as the Western Antarctic Peninsula, both long-term and occasional acute temperature rises will impact species found there, and it has become crucial to understand the capacity of these species to respond to such thermal stress. Here, we use the Antarctic sponge Isodictya sp. to investigate how sessile organisms (particularly Porifera) can adjust to acute short-term heat stress, by exposing this species to 3 and 5 °C for 4 h, corresponding to predicted temperatures under high-end 2080 IPCC-SRES scenarios. Assembling a de novo reference transcriptome (90,188 contigs, >93.7% metazoan BUSCO genes) we have begun to discern the molecular response employed by Isodictya to adjust to heat exposure. Our initial analyses suggest that TGF-β, ubiquitin and hedgehog cascades are involved, alongside other genes. However, the degree and type of response changed little from 3 to 5 °C in the time frame examined, suggesting that even moderate rises in temperature could cause stress at the limits of this organism’s capacity. Given the importance of sponges to Antarctic ecosystems, our findings are vital for discerning the consequences of short-term increases in Antarctic ocean temperature on these and other species.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5364-5364
Author(s):  
Henning D. Popp ◽  
Vanessa Kohl ◽  
Johanna Flach ◽  
Susanne Brendel ◽  
Helga Kleiner ◽  
...  

The accumulation of DNA damage and the alteration of the DNA damage response (DDR) are critical features of genetic instability that is presumed to be implicated in BCR/ABL1-mediated blastic transformation of chronic myeloid leukemia (CML). The aim of our study was to analyze underlying mechanisms of genetic instability with regard to DNA damage such as DNA double-strand breaks (DSB), DSB repair and DDR signaling during blastic transformation of CML. Immunofluorescence microscopy of γH2AX was performed for quantification of DSB in peripheral blood mononuclear cells (PBMC) of 8 healthy individuals, 24 chronic phase (CP)-CML patients under current/discontinued tyrosine kinase inhibitor (TKI) treatment (21 patients in deep molecular response (DMR), 3 patients in major molecular response (MMR)), 5 CP-CML patients under current/discontinued TKI treatment with loss of MMR, 3 de novo non-treated CP-CML patients and 2 blast phase (BP)-CML patients. In addition, immunofluorescence microscopy of γH2AX/53BP1 was used for semi-quantification of error-prone DSB repair. Furthermore, immunoblotting of p-ATM, p-ATR, p-CHK1, p-CHK2 and p-TP53 was performed in PBMC of CML patients in comparison to PBMC of healthy individuals. Our analysis revealed an increase in numbers of γH2AX foci in PBMC of CP-CML patients under current/discontinued TKI treatment with loss of MMR (1.8 γH2AX foci per PBMC ± 0.4), in PBMC of de novo non-treated CP-CML patients (2.3 γH2AX foci per PBMC ± 0.7) and in PBMC of BP-CML patients (4.9 γH2AX foci per PBMC ± 0.9) as compared to the number of γH2AX foci in PBMC of healthy individuals (1.0 γH2AX foci per PBMC ± 0.1) and in PBMC of CP-CML patients under current/discontinued TKI treatment in DMR/MMR (1.0 γH2AX foci per PBMC ± 0.1) (Figure 1A and B). Analysis of co-localizing γH2AX/53BP1 foci in PBMC suggested progressive activation of error-prone nonhomologous end-joining repair mechanisms during blastic transformation in CML. Signatures of p-ATM, p-ATR, p-CHK1, p-CHK2 and p-TP53 indicated alterations of the DDR. In summary, our data provide evidence for an accumulation of DNA damage in PBMC of CML patients towards BP-CML patients. We hypothesize that ongoing DSB generation, error-prone DSB repair and DDR alterations might be critical mechanisms of blastic transformation in CML. Figure 1 Analysis of γH2AX foci in freshly isolated peripheral blood mononuclear cells (PBMC) of healthy individuals and chronic myeloid leukemia (CML) patients. (A) Exemplary immunofluorescence microscopic images of γH2AX foci (green, Alexa 488) and cell nuclei (blue, DAPI) in PBMC of a healthy individual (HEALTHY#3), a chronic phase CML patient with a deep molecular response to tyrosine kinase inhibitor (CP-CML DMR#16), a de novo non-treated chronic phase CML patient (CP-CML#1) and a blast phase CML patient (BP-CML#2). (B) γH2AX foci levels in PBMC of healthy individuals and in PBMC of CML patients. Figure 1 Disclosures Saussele: Pfizer: Honoraria; Novartis: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Fabarius:Novartis: Research Funding.


2019 ◽  
Author(s):  
Rui Xiong ◽  
Liu Chengli ◽  
Min Xu ◽  
Shuang-Shuang Wei ◽  
Hua Tang

Abstract Background Pitayas are currently attracting considerable interest as a fruit with many health benefits. However, the lack of natural light after November in Hainan, China, severely restricts the production of pitaya in winter. To further explore the molecular mechanisms regulating flowering in pitaya, we used de novo RNA sequencing-based transcriptomic analysis for four stages of pitaya subjected to light induction. Results We assembled 68113 unigenes in total, comprising 29782 unigenes with functional annotations in the NR database, 20716 annotations in SwissProt, 18088 annotations in KOG, and 11059 annotations in KEGG. Comparison between different samples revealed different numbers of significantly differentially expressed genes (DEGs). A number of DEGs involved in energy metabolism-related processes and plant hormones were detected. Moreover, we discovered many CONSTANS-LIKE, FLOWERING LOCUS T and other DEGs involved in direct regulation of flowering, along with CDF and TCP, which function as typical transcription factor genes in the flowering process. At the transcriptomic level, we confirmed 13 DEGs with different functions in the time-course response to light-induced flowering by quantitative reverse-transcription PCR analysis. Conclusions These DEGs may include some key genes that control the floral-induction network, increasing our understanding of the molecular mechanism of floral regulation in pitaya. These findings will also aid the development of biotechnologies aimed at creating a variant of pitaya that is less sensitive to light conditions and blooms throughout the year.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2521
Author(s):  
Gabriel Etienne ◽  
Stéphanie Dulucq ◽  
Fréderic Bauduer ◽  
Didier Adiko ◽  
François Lifermann ◽  
...  

Background: Tyrosine Kinase Inhibitors (TKIs) discontinuation in patients who had achieved a deep molecular response (DMR) offer now the opportunity of prolonged treatment-free remission (TFR). Patients and Methods: Aims of this study were to evaluate the proportion of de novo chronic-phase chronic myeloid leukemia (CP-CML) patients who achieved a sustained DMR and to identify predictive factors of DMR and molecular recurrence-free survival (MRFS) after TKI discontinuation. Results: Over a period of 10 years, 398 CP-CML patients treated with first-line TKIs were included. Median age at diagnosis was 61 years, 291 (73%) and 107 (27%) patients were treated with frontline imatinib (IMA) or second- or third-generation TKIs (2–3G TKI), respectively. With a median follow-up of seven years (range, 0.6 to 13.8 years), 182 (46%) patients achieved a sustained DMR at least 24 months. Gender, BCR-ABL1 transcript type, and Sokal and ELTS risk scores were significantly associated with a higher probability of sustained DMR while TKI first-line (IMA vs. 2–3G TKI) was not. We estimate that 28% of CML-CP would have been an optimal candidate for TKI discontinuation according to recent recommendations. Finally, 95 (24%) patients have entered in a TFR program. MRFS rates at 12 and 48 months were 55.1% (95% CI, 44.3% to 65.9%) and 46.9% (95% CI, 34.9% to 58.9%), respectively. In multivariate analyses, first-line 2–3G TKIs compared to IMA and TKI duration were the most significant factors of MRFS. Conclusions: Our results suggest that frontline TKIs have a significant impact on TFR in patients who fulfill the selection criteria for TKI discontinuation.


PLoS ONE ◽  
2019 ◽  
Vol 14 (8) ◽  
pp. e0216267
Author(s):  
Samarth ◽  
Robyn Lee ◽  
Jiancheng Song ◽  
Richard C. Macknight ◽  
Paula E. Jameson

Blood ◽  
2005 ◽  
Vol 106 (7) ◽  
pp. 2520-2526 ◽  
Author(s):  
Deborah White ◽  
Verity Saunders ◽  
A. Bruce Lyons ◽  
Susan Branford ◽  
Andrew Grigg ◽  
...  

AbstractMost patients with de novo chronic myeloid leukemia (CML) achieve good responses to imatinib, but the rate and degree of molecular response is variable. We assessed the inhibitory concentration 50% for imatinib (IC50imatinib) in 62 patients with de novo chronic-phase CML as a predictor of molecular response. IC50imatinib was determined in pretherapy blood samples by measuring the in vitro imatinib-induced reduction of the phosphorylated form of the adaptor protein Crkl (CT10 regulator of kinase like). There was marked variability between patients, with IC50imatinib ranging from 0.375 to 1.8 μM (median, 0.6 μM). Patients with low IC50imatinib (IC50 ≤ 0.6 μM; n = 36) had a 36% probability of achieving 2-log reduction in BCR-ABL (breakpoint cluster region-abelson) by 3 months compared with 8% in patients with high IC50imatinib (n = 26) (P = .01). The IC50imatinib was also predictive of molecular response at 12 months, with 47% of patients in the low IC50imatinib group achieving 3-log reduction and 23% in the high IC50imatinib group (P = .03). The predictive power of IC50imatinib was particularly strong in patients with low Sokal scores. These data provide strong evidence that intrinsic sensitivity to imatinib is variable in previously untreated patients with CML, and the actual level of BCR-ABL kinase inhibition achieved is critical to imatinib response. The IC50imatinib potentially provides a new prognostic indicator for molecular response in patients treated with imatinib. (Blood. 2005; 106:2520-2526)


2014 ◽  
Vol 33 (10) ◽  
pp. 1723-1735 ◽  
Author(s):  
Hong-Na Zhang ◽  
Yong-Zan Wei ◽  
Ji-Yuan Shen ◽  
Biao Lai ◽  
Xu-Ming Huang ◽  
...  

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