Immune associated LncRNAs identify novel prognostic subtypes of renal clear cell carcinoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148402/1/mc22949_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148402/2/mc22949.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148402/3/mc22949-sup-0001-SuppData-S1.pd

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

Acute-on-Chronic Liver Failure (ACLF): The ‘Kyoto Consensus’-Steps From Asia

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the APASL ACLF Research Consortium (AARC) was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the \u27Golden Therapeutic Window\u27, the \u27transplant window\u27, and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The \u27Kyoto APASL Consensus\u27 presented below carries the final recommendations along with the relevant background information and areas requiring future studies

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Effect of Date of Sowing and Nitrogen Levels on Spot Blotch Disease of Wheat Caused by Bipolaris sorokiniana

In India, wheat is grown in the Rabi season mostly under irrigated condition. The main constraints responsible for less yield of wheat in comparison to other country seem to non-availability of seeds of improved high yielding varieties to farmers, poor fertility, unirrigated land and other inputs. Experimental findings clearly indicates that yield loss due to spot blotch varied between 7 to 30 per cent and loss in 1000-grain weight between 3 to 23 per cent, depending upon the levels of disease. Delayed sowing favored incidence of spot blotch irrespective of nitrogen level and more disease developed at higher nitrogen level in all the three date of sowing. Higher levels of nitrogen at all the three date of sowing increased yield and 1000-grain weight and with delay in sowing, yield and 1000-grain weight decreased significantly at all the three nitrogen level.</jats:p

Efficacy of Fungicides against Bipolaris sorokiniana under in vitro and in vivo Conditions

Spot blotch of wheat caused by Bipolaris sorokiniana could be effectively and economically controlled by two foliar sprays of either Propiconazole or Hexaconazole @ 0.1 per cent at fifteen days interval but on the basis of cost- benefit ratio Hexaconazole had an edge over Propiconazole. The harmful effects of fungicides to human and environment, there have been proved useful and economical in the control of spot blotch. Non systemic and systemic foliar fungicides belonging to the dithiocarbamate and Triazoles are found to be effective. Foliar applications of systemic fungicides between heading and grain filling stages, are cost effective. Propiconazole, Hexaconazole and Difenaconazole + Propiconazole at 250 ppm completely inhibited the mycelial growth of B. sorokiniana. Carbendazim and Copper oxychloride also causes and complete inhibition but at 500 and 1000 ppm, respectively but Mancozeb could not give complete inhibition even at 1000 ppm

Efficacy of Fungicides against Bipolaris sorokiniana under in vitro and in vivo Conditions

Spot blotch of wheat caused by Bipolaris sorokiniana could be effectively and economically controlled by two foliar sprays of either Propiconazole or Hexaconazole @ 0.1 per cent at fifteen days interval but on the basis of cost- benefit ratio Hexaconazole had an edge over Propiconazole. The harmful effects of fungicides to human and environment, there have been proved useful and economical in the control of spot blotch. Non systemic and systemic foliar fungicides belonging to the dithiocarbamate and Triazoles are found to be effective. Foliar applications of systemic fungicides between heading and grain filling stages, are cost effective. Propiconazole, Hexaconazole and Difenaconazole + Propiconazole at 250 ppm completely inhibited the mycelial growth of B. sorokiniana. Carbendazim and Copper oxychloride also causes and complete inhibition but at 500 and 1000 ppm, respectively but Mancozeb could not give complete inhibition even at 1000 ppm.</jats:p

Effect of Date of Sowing and Nitrogen Levels on Spot Blotch Disease of Wheat Caused by Bipolaris sorokiniana

In India, wheat is grown in the Rabi season mostly under irrigated condition. The main constraints responsible for less yield of wheat in comparison to other country seem to non-availability of seeds of improved high yielding varieties to farmers, poor fertility, unirrigated land and other inputs. Experimental findings clearly indicates that yield loss due to spot blotch varied between 7 to 30 per cent and loss in 1000-grain weight between 3 to 23 per cent, depending upon the levels of disease. Delayed sowing favored incidence of spot blotch irrespective of nitrogen level and more disease developed at higher nitrogen level in all the three date of sowing. Higher levels of nitrogen at all the three date of sowing increased yield and 1000-grain weight and with delay in sowing, yield and 1000-grain weight decreased significantly at all the three nitrogen level