Temporal transcriptome of tomato elucidates the signaling pathways of induced systemic resistance and systemic acquired resistance activated by Chaetomium globosum

C. globosum is an endophytic fungus, which is recorded effective against several fungal and bacterial diseases in plants. The exclusively induce defense as mechanism of biocontrol for C. globosum against phyto-pathogens is reported. Our pervious study states the effectiveness of induced defense by C. globosum (Cg), in tomato against Alternaria solani. In this study the temporal transcriptome analysis of tomato plants after treatment with C. globosum was performed for time points at 0 hpCi, 12 hpCi, 24 hpCi and 96 phCi. The temporal expression analysis of genes belonging to defense signaling pathways indicates the maximum expression of genes at 12 h post Cg inoculation. The sequential progression in JA signaling pathway is marked by upregulation of downstream genes (Solyc10g011660, Solyc01g005440) of JA signaling at 24 hpCi and continued to express at same level upto 96 hpCi. However, the NPR1 (Solyc07g040690), the key regulator of SA signaling is activated at 12 h and repressed in later stages. The sequential expression of phenylpropanoid pathway genes (Solyc09g007920, Solyc12g011330, Solyc05g047530) marks the activation of pathway with course of time after Cg treatment that results in lignin formation. The plant defense signaling progresses in sequential manner with time course after Cg treatment. The results revealed the involvement of signaling pathways of ISR and SAR in systemic resistance induced by Cg in tomato, but with temporal variation

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri.

Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia) and colon (E. histolytica) causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide

Key HMBC correlations of compound 9.

<p>The 3D energy minimized conformer was generated using BIOVIA Discovery Studio 2017 software.</p

Percent inhibition of <i>N</i>. <i>fowleri</i> and human HUVEC cell proliferation by 1 and 2.

<p>(A) The EC₅₀ dose response curves for <b>1</b> and <b>2</b> against <i>N</i>. <i>fowleri</i> trophozoites. (B) The EC₅₀ dose response curves for <b>1</b> and <b>2</b> against HUVEC cells. (C) Compound <b>1</b> and <b>2</b> displayed more potent inhibition of <i>N</i>. <i>fowleri</i> proliferation compared to HUVEC cells, which was statistically significant by Student’s t test analysis.</p

¹H (400 MHz) and ¹³C NMR (100 MHz) data for 8 compared to the crude reported ¹H NMR data ((CD₃)₂CO) ^a.

<p>¹H (400 MHz) and ¹³C NMR (100 MHz) data for 8 compared to the crude reported ¹H NMR data ((CD₃)₂CO) <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005832#t001fn001" target="_blank">^a</a>.</p