Fusarium head blight (FHB) caused by Fusarium graminearum (Fg) is a devastating disease of crops, especially wheat and barley, resulting in significant yield loss and reduced grain quality. Fg ...infection leads to the production of mycotoxins, whose consumption is toxic to humans and livestock. The Arabidopsis DMR6 gene encodes a putative 2-oxoglutarate Fe(II)-dependent oxygenase (2OGO) and has been identified as a susceptibility factor to downy mildew. We generated site-specific mutations in Arabidopsis At2OGO by CRISPR/Cas9 gene editing. The resulting At2OGO knock-out (KO) mutants display enhanced resistance to Fg in a detached inflorescence infection assay. Expression profiling of defense genes revealed that impairment of At2OGO function resulted in the upregulation of defense genes that are regulated by salicylic acid (SA), jasmonic acid (JA) and ethylene (ET) pathways. Complementation of the At2OGO-KO lines with a barley (cv. Conlon) orthologue, Hv2OGO, restored susceptibility to Fg. This result indicates that the Hv2OGO gene is functionally equivalent to its Arabidopsis counterpart and, hence, may have a similar role in conditioning susceptibility to FHB in barley. These results provide a molecular basis for proposing 2OGO as a plant immunity suppressor in Arabidopsis and potentially in barley plants and establish a rationale and strategy for enhancing FHB resistance in barley.
Fusarium head blight (FHB) caused by Fusarium graminearum (Fg) severely affects cereal crops, especially wheat and barley. FHB results in significant yield loss, reduces grain quality and ...contaminates grains with mycotoxin. The development of FHB-resistant cereal cultivars can be expedited through CRISPR gene editing. The Arabidopsis ethylene insensitive 2 (AtEIN2) plays a key role in ethylene signaling pathway and is critical for monitoring plant growth and defense responses. RNAi down-regulation of the wheat homolog TaEIN2 has been shown to enhance wheat FHB resistance. Here we generated site-specific mutations in AtEIN2 by CRISPR-editing. Detached inflorescence infection assays revealed that AtEIN2 knock-out (KO) mutants displayed enhanced Fg resistance and substantially reduced Fg spore production in planta. Gene expression profiling of defense genes revealed that impairment of AtEIN2 resulted in down-regulation of the ethylene signaling pathway while the salicylic acid signaling pathway was unaffected. Complementation of AtEIN2-KO plants with a barley orthologue, HvEIN2, restored Fg susceptibility, indicating that HvEIN2 is functionally equivalent to its Arabidopsis counterpart and, hence, may have a similar role in conditioning barley Fg susceptibility. These results provide insight into the defense role of EIN2 and a molecular and functional foundation for manipulating HvEIN2 to enhance FHB resistance in barley.
•Arabidopsis AtEIN2-KO mutants were produced by CRISPR-gene editing.•Arabidopsis AtEIN2-KO mutants were highly resistant to F. graminearum infection.•AtEIN2-KO mutant complemented with barley HvEIN2 regained Fg susceptibility.•New insights on the involvement of ethylene signaling in Fg-host interaction.
A direct comparison of endovascular versus microsurgical treatment of ruptured middle cerebral artery (MCA) aneurysms in randomized trials is lacking. As endovascular treatment strategies continue to ...evolve, the number of reports of endovascular treatment of these lesions is increasing. Herein, the authors report a detailed post hoc analysis of ruptured MCA aneurysms treated by microsurgical clipping from the Barrow Ruptured Aneurysm Trial (BRAT).
The cases of patients enrolled in the BRAT who underwent microsurgical clipping for a ruptured MCA aneurysm were reviewed. Characteristics of patients and their clinical outcomes and long-term angiographic results were analyzed.
Fifty patients underwent microsurgical clipping of a ruptured MCA aneurysm in the BRAT, including 21 who crossed over from the endovascular treatment arm. Four patients with nonsaccular (e.g., dissecting, fusiform, or blister) aneurysms were excluded, leaving 46 patients for analysis. Most (n = 32; 70%) patients presented with a Hunt and Hess grade II or III subarachnoid hemorrhage, with a high prevalence of intraparenchymal blood (n = 23; 50%), intraventricular blood (n = 21; 46%), or both. At the last follow-up (up to 6 years after treatment), clinical outcomes were good (modified Rankin Scale score 0–2) in 70% (n = 19) of 27 Hunt and Hess grades I–III patients and in 36% (n = 4) of 11 Hunt and Hess grade IV or V patients. There were no instances of rebleeding after the surgical clipping of aneurysms in this series at the time of last clinical follow-up.
Microsurgical clipping of ruptured MCA aneurysms has several advantages over endovascular treatment, including durability over time. The authors report detailed outcome data of patients with ruptured MCA aneurysms who underwent microsurgical clipping as part of a prospective, randomized trial. These results should be used for comparison with future endovascular and surgical series to ensure that the best results are being achieved for patients with ruptured MCA aneurysms.
Vitamin B12 deficiency can lead to oxidative stress, which is known to be involved in neurodegenerative diseases such as Alzheimer's disease (AD). Mogrosides are plant-derived triterpene glycosides ...that exhibit anti-inflammatory and antioxidant activity in animal cell lines and mouse models. Since amyloid-β toxicity is known to cause oxidative stress and damage to brain cells, we hypothesized that mogrosides may have a protective effect against AD. In this study, we investigated the potential anti-AD effect of mogrosides in vitamin B12-deficient wild-type N2 and in transgenic CL2355
expressing amyloid-β peptide. Our data indicated that mogrosides have a beneficial effect on the lifespan and egg-laying rate of N2 and vitamin B12-deficient N2 worms. Additionally, the results revealed that mogrosides can effectively delay the paralysis of CL2355 worms as determined by serotonin sensitivity assay. Our analysis showed that mogrosides increase the expression of oxidative protective genes in N2 worms fed with vitamin B12-deficient OP50 bacterium. We conclude that mogrosides may exert preventative rather than curative effects that counteract the detrimental vitamin B12-deficient environment in N2 and CL2355
by modulating oxidation-related gene expression.
Anterior cerebral artery (ACA) bypasses for complex aneurysms are infrequently performed, yet previous experience demonstrates the importance of intracranial-intracranial bypasses. Here we describe ...technical advances in intracranial-intracranial bypass techniques and their clinical results.
Twenty-three patients with complex aneurysms requiring ACA bypasses were retrospectively studied. Ten patients were treated in period 1 (1997–2013) and 13 in period 2 (2014–2018).
There were 3 precommunicating, 8 communicating, and 8 postcommunicating ACA aneurysms, plus 4 middle cerebral artery aneurysms. ACA in situ bypass was the most commonly performed (9 patients; 39%). The classic left A3 ACA–right A3 ACA in situ bypass was performed in 5 patients, but 3 new in situ variations emerged in period 2: left pericallosal artery (PcaA)–right PcaA (n = 1), left callosomarginal artery (CmaA)–right CmaA (n = 2), and left CmaA–right A3 ACA (n = 1). The sole reimplantation in period 1 was the ipsilateral and vertical PcaA-CmaA reimplantation, whereas reimplantations in period 2 were contralateral and horizontal (left PcaA–right PcaA and right A3 ACA–left anterior internal frontal artery). The A1 ACA was used as a donor only in period 2 in 4 patients with middle cerebral artery bifurcation aneurysms. Bypass patency was 91%, and 21 patients (91%) improved or remained at neurologic baseline (mean standard deviation follow-up duration, 26 8.2 months).
ACA bypass techniques continue to evolve with the addition of several variations. These variations push bypass techniques beyond the standard constructs and add important alternatives to our bypass arsenal.
The limited symptom relief and side effects of current Alzheimer's disease (AD) medications warrant urgent discovery and study of new anti-AD agents. The "cholinergic hypothesis" of AD prompts us to ...search for plant-derived acetylcholineesterase (AChE) inhibitors such as galanthamine that has been licensed in Europe for AD treatment. We used the unique amyloid β-expressing transgenic C. elegans CL4176, which exhibits paralysis when human Aβ1-42 is induced, to study two natural benzylphenethylamine alkaloids isolated from Lycoris radiata (L' Her.) Herb, galanthamine and haemanthidine, and their synthetic derivatives 1,2-Di-O-acetyllycorine and 1-O-acetyllycorine for their anti-paralysis effects. Our data indicate that these Lycoris compounds effectively delay the paralysis of CL4176 worms upon temperature up-shift, and prolong the lives of these transgenic worms. Lycoris compounds were shown to significantly inhibit the gene expression of ace-1 and ace-2. Additionally, the Lycoris compounds may modulate inflammatory and stress-related gene expressions to combat the Aβ-toxicity in C. elegans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The objective of this study was to evaluate the existing Spetzler-Martin (SM), Spetzler-Ponce (SP), and Lawton-Young (LY) grading systems for cerebellar arteriovenous malformations (AVMs) and to ...propose a new grading system to estimate the risks associated with these lesions.
Data for patients with cerebellar AVMs treated microsurgically in two tertiary medical centers were retrospectively reviewed. Data from patients at institution 1 were collected from September 1999 to February 2013, and at institution 2 from October 2008 to October 2015. Patient outcomes were classified as favorable (modified Rankin Scale mRS score 0-2) or poor (mRS score 3-6) at the time of discharge. Using chi-square and logistic regression analysis, variables associated with poor outcomes were assigned risk points to design the proposed grading system. The proposed system included neurological status prior to treatment (poor, +2 points), emergency surgery (+1 point), age > 60 years (+1 point), and deep venous drainage (deep, +1 point). Risk point totals of 0-1 comprised grade 1, 2-3 grade 2, and 4-5 grade 3.
A total of 125 cerebellar AVMs of 1328 brain AVMs were reviewed in 125 patients, 120 of which were treated microsurgically and included in the study. With our proposed grading system, we found poor outcomes differed significantly between each grade (p < 0.001), while with the SM, SP, and LY grading systems they did not (p = 0.22, p = 0.25, and p = 1, respectively). Logistic regression revealed grade 2 had 3.3 times the risk of experiencing a poor outcome (p = 0.008), while grade 3 had 9.9 times the risk (p < 0.001). The proposed grading system demonstrated a superior level of predictive accuracy (area under the receiver operating characteristic curve AUROC of 0.72) compared with the SM, SP, and LY grading systems (AUROC of 0.61, 0.57, and 0.51, respectively).
The authors propose a novel grading system for cerebellar AVMs based on emergency surgery, venous drainage, preoperative neurological status, and age that provides a superior prognostication power than the formerly proposed SM, SP, and LY grading systems. This grading system is clinically predictive of patient outcomes and can be used to better guide vascular neurosurgeons in clinical decision-making.
Abstract
Differentiation of pluripotent stem cells into functional parathyroid-like cells would accelerate development of important therapeutic options for subjects with parathyroid-related ...disorders, from the design and screening of novel pharmaceutical agents to the development of durable cellular therapies. We have established a highly reproducible directed differentiation approach leading to PTH-expressing cells from human embryonic stem cells and induced pluripotent stem cells. We accomplished this through the comparison of multiple different basal media, the inclusion of the CDK inhibitor PD0332991 in both definitive endoderm and anterior foregut endoderm stages, and a 2-stage pharyngeal endoderm series. This is the first protocol to reproducibly establish PTH-expressing cells from human pluripotent stem cells and represents a first step toward the development of functional parathyroid cells with broad applicability for medicinal and scientific investigation.
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