Seed development was investigated in kernels of developing wild-type and viviparous (vp-1) Zea mays L. Embryos and endosperm of wild-type kernels began to dehydrate at approx. 35 d after pollination ...(DAP); viviparous embryos did not desiccate but accumulated fresh weight via coleoptile growth in the caryopses. Concentrations of endogenous abscisic acid (ABA) in the embryo were relatively high early in development, being approx. 150 ng·g-1 fresh weight at 20 DAP. The ABA content declined thereafter, falling to approx. 50 ng·g-1 at 30 DAP. Endosperm ABA content was always low, being less than 20 ng·g-1. There were no differences between wild-type and vp-1 tissues. Immature kernels did not germinate when removed from the ear until late in development. The ability to germinate was correlated with decreasing moisture content in the endosperm at the time of removal; premature drying of immature kernels resulted in greatly increased germination following imbibition. Excised embryos germinated precociously when removed from the endosperm as early as 25 DAP. Such germination could be prevented by treatment with 10-5 M ABA or by lowering the solute potential (Ψs) of the medium with 0.3 M mannitol. Treatment of excised embryos with ABA led to internal ABA concentrations comparable to those in embryos in which germination was inhibited in situ. Mannitol treatment did not have this effect, although water-deficit stress of excised embryos resulted in substantial ABA production. Germinated vp-1 embryos were less sensitive to growth inhibition by ABA or mannitol than germinating wild-type embryos. The vp-1 seedlings were not wilty and their transpiration rates were reduced in response to ABA or water shortage.
Organic farming aims to stimulate soil fertility by avoiding the use of synthetic fertiliser inputs, relying instead on locally available natural resources. It is regarded by many as a sustainable ...alternative to conventional fanning because it ensures higher biodiversity, restricts environmental pollution, prevents land degradation and is easy to apply for smallholder and subsistence farmers. Although widely practiced and studied in temperate regions, little is known about the potential overall benefits of organic farming in the tropics and subtropics. This paper addresses this gap by undertaking an analysis of the differences between organic and conventional agriculture in the tropics and sub-tropics based on an extensive literature review including 88 papers with 458 data pairs. The comparison is based on three main indicators： yield, gross margin and soil organic carbon （SOC）. The differences between the organic and conventional systems for each of these main indicators is represented by the ratio of the value of the indicator in the organic system divided by the corresponding value in the conventional system. This was initially calculated for each data pair individually, and grouped by a variety of explanatory factors, such as precipitation, human development level, soil texture, crop type, organic input type, time after conversion and certification. The results demonstrate that under organic management, yields were on average 26% higher, gross margins 51% higher and soil organic carbon 53% higher than under conventional management. The highest yield increases in organic cropping systems were achieved in the least developed countries, in arid regions and on coarse soils. For gross margins, certification was the main reason for differences between organic and conventional systems. Certified farmers, mostly located in developed countries, receive significantly higher prices. Furthermore, organic farming in the driest regions results in higher profits than in other regions. Even though soil organic carbon was significantly higher overall under organic management, the results do not show significant differences when grouped by the explanatory factors. They do however suggest that the highest carbon sequestration potential occurs in systems that had a high level of inputs, in regions with 1000-1 500 mm of rainfall and on clayey soils.
Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. ...We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown. To test this idea, we correlated the sensitivity patterns of 481 compounds with ∼19,000 basal transcript levels across 823 different human cancer cell lines and identified selective outlier transcripts. This process yielded many novel mechanistic insights, including the identification of activation mechanisms, cellular transporters and direct protein targets. We found that ML239, originally identified in a phenotypic screen for selective cytotoxicity in breast cancer stem-like cells, most likely acts through activation of fatty acid desaturase 2 (FADS2). These data and analytical tools are available to the research community through the Cancer Therapeutics Response Portal.
Cancer is often seen as a disease of mutations and chromosomal abnormalities. However, some cancers, including pediatric rhabdoid tumors (RTs), lack recurrent alterations targetable by current drugs ...and need alternative, informed therapeutic options. To nominate potential targets, we performed a high-throughput small-molecule screen complemented by a genome-scale CRISPR-Cas9 gene-knockout screen in a large number of RT and control cell lines. These approaches converged to reveal several receptor tyrosine kinases (RTKs) as therapeutic targets, with RTK inhibition effective in suppressing RT cell growth in vitro and against a xenograft model in vivo. RT cell lines highly express and activate (phosphorylate) different RTKs, creating dependency without mutation or amplification. Downstream of RTK signaling, we identified PTPN11, encoding the pro-growth signaling protein SHP2, as a shared dependency across all RT cell lines. This study demonstrates that large-scale perturbational screening can uncover vulnerabilities in cancers with “quiet” genomes.
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•Rhabdoid cell lines and tumors have few mutations yet highly express a range of RTKs•RTKs and SHP2 are vulnerabilities in small-molecule and CRISPR-knockout screens•RTK inhibitors are effective against a xenografted rhabdoid mouse model in vivo•Perturbational screens may identify vulnerabilities not detectable in genomic analyses
Using a diverse set of rhabdoid tumor cell lines and both small-molecule and CRISPR-Cas9 gene-knockout screening, Oberlick et al. find high expression and dependency upon a wide range of receptor tyrosine kinases (RTKs) and SHP2 downstream. These RTK inhibitors are also effective against a rhabdoid tumor mouse model.
In the intensive care unit, dopamine agonists (DA) have been used in traumatic brain injury (TBI) patients to augment or accelerate cognitive recovery and rehabilitation. However, the efficacy and ...safety of DA in this population is not well established. We conducted a systematic review of randomized controlled trials (RCTs) examining the clinical efficacy and safety of DA in patients with TBI. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, comparing DA to either placebo, standard treatment, or another active comparator. There was no restriction for age, date, or language of publication. Sensitivity analyses were planned to evaluate the potential effect of timing of TBI, age, drugs, and year of publication on efficacy. Among the 790 citations identified, 20 RCTs evaluating methylphenidate, amantadine, and bromocriptine were eligible. Significant clinical heterogeneity was observed between and within studies, which precluded any pooling of data. Efficacy outcomes included mainly neuropsychological measures of cognitive functioning. A total of 76 different neuropsychological tests were used, but most of them (59%) only once. Only 5 studies systematically assessed safety. No trend could be drawn from the analysis of efficacy and safety. Important sources of bias in the studies were of major concern. Considering the absence of consensus regarding clinical outcome, the lack of safety assessment, and the high risk of bias in the included trials, more research is warranted before DA can be recommended in critically ill TBI patients.
Angiosarcoma is a malignant tumor of vascular endothelial cells that arises in the head and neck. It is a rare, difficult to treat, and lethal tumor.
Clinical data from patients who were diagnosed ...with angiosarcoma of the scalp between 1975 and 2002 at the University of Michigan were reviewed. Analysis was performed to assess for factors impacting time to recurrence and survival.
The study was comprised of 29 patients with a median age of 71.0 years. Most patients presented after a delay in diagnosis with either a bruise-like macule (48.3%) or a nonbruise-like nodule (51.7%). Seventy-five percent of patients had pathologic Stage T2 disease, and 76% of patients had high-grade tumors. Virtually all patients underwent surgical excision (96.6%); however, negative surgical margins were achieved in only 21.4% of patients. Multiple lesions on presentation were associated with a shorter time to recurrence (P = 0.02). The median actuarial survival was 28.4 months. Younger patients and patients with Stage T1 disease had improved survival (P = 0.024 and P = 0.013, respectively). Radiation therapy was associated significantly with a decreased chance of death (hazard ratio, 0.16; P = 0.006).
Although surgery remains the first option for the treatment of patients with angiosarcoma of the scalp, achieving negative margins often is impossible. Patients who are younger and who have less extensive disease fare better. Postoperative radiation therapy should be employed routinely, as it may lead to improved survival.
The aim of this study was to produce an economic cost model comparing the use of the Medaphor ScanTrainer virtual reality training simulator for obstetrics and gynaecology ultrasound to achieve basic ...competence, with the traditional training method. A literature search and survey of expert opinion were used to identify resources used in training. An executable model was produced in Excel. The model showed a cost saving for a clinic using the ScanTrainer of £7114 per annum. The uncertainties of the model were explored and it was found to be robust. Threshold values for the key drivers of the model were identified. Using the ScanTrainer is cost saving for clinics with at least two trainees per year to train, if it would take at least six lists to train them using the traditional training method and if a traditional training list has at least two fewer patients than a standard list.
To determine if 3-T magnetic resonance (MR) spectroscopy allows accurate distinction of recurrent tumor from radiation effects in patients with gliomas of grade II or higher.
This blinded prospective ...study included 14 patients who underwent in vivo 3-T MR spectroscopy prior to stereotactic biopsy. All patients received a previous diagnosis of glioma (grade II or higher) and high-dose radiation therapy (>54 Gy). Prior to MR spectroscopy, conventional MR imaging was performed at 1.5 T to identify a gadolinium-enhanced region within the irradiated volume. Diagnosis was assigned by means of histopathologic analysis of the biopsy samples.
Sixteen of 17 biopsy locations could be classified as predominantly tumor or predominantly radiation effect on the basis of the ratio of choline at the biopsy site to normal creatine level by using a value greater than 1.3 as the criterion for tumor. The remaining case, classified as recurrent tumor on the basis of MR spectroscopy results, was diagnosed as predominantly radiation effect on the basis of histopathologic findings. Disease in this patient progressed to biopsy-proven recurrence within 3 months. Overall, the ratio of choline at the biopsy site to normal creatine level was significantly elevated (unpaired two-tailed Student t test, P <.002) in those biopsy samples composed predominantly of tumor (n = 9) compared with those containing predominantly radiation effects (n = 8). The ratio was not significantly different between the two histopathologic groups.
In vivo 3-T MR spectroscopy has sufficient spatial resolution and chemical specificity to allow distinction of recurrent tumor from radiation effects in patients with treated gliomas.
A deficiency of nitric oxide may be responsible for the increased vascular resistance associated with human essential hypertension and that seen in animal models of hypertension. Premenopausal ...females are relatively protected from hypertension and cardiovascular complications. Levels of superoxide can influence the availability of nitric oxide. We hypothesize that there are differences in nitric oxide availability between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) and that superoxide may be responsible for at least some of these differences. We studied vascular reactivity in endothelium-intact aortic rings from WKY and SHRSP. We measured nitric oxide synthase activity in endothelial cells removed from aortas and also measured circulating nitrite/nitrate levels. We found the response to N(G)-nitro-L-arginine methyl ester to be significantly greater in WKY compared with SHRSP (95% CI: 20 to 174; P=.015) and in females compared with males in WKY (95% CI: 143 to 333; P=.00004) and SHRSP (95% CI: 70 to 224; P=.0006). Endothelial nitric oxide synthase activity was significantly greater in SHRSP compared with WKY (95% CI: 2.3 to 17.6; P=.016). The EC50 for relaxation to carbachol was significantly greater in male rats compared with female rats (95% CI: -1.1 to -0.2; P=.003) within the SHRSP strain. The maximum relaxation to carbachol was significantly attenuated in stroke prone spontaneously hypertensive compared with Wistar-Kyoto rats (95% CI: 1.7 to 14.4; P=.015). Diethyldithiocarbamate had a significantly greater effect on the stroke prone spontaneously hypertensive rats' carbachol response than that of Wistar-Kyoto rats (95% CI: 14.3 to 47.0; P=.0008). We conclude that superoxide may be responsible for strain differences in vascular reactivity, whereas nitric oxide availability may be responsible for sex differences independently of endothelial nitric oxide synthase activity and superoxide.
Purpose.
To determine whether a mixed course on the Oxford unicompartmental knee arthroplasty (UKA) could improve the non-technical (cognitive) skills of performing UKA.
Methods.
120 delegates ...consisting of consultant orthopaedic surgeons and advanced surgical trainees attended a 2-day course. 104 (87%) of the delegates had performed total knee arthroplasties, whereas 79 (66%) had performed UKAs. The course consisted of didactic lectures, interactive surgical demonstrations, and practical dry-bone skills workshops. Cognitive skills were assessed at the start (day 1) and end (day 2) of the course using 10 multiple-choice questions. The maximum test score was 10. Multilevel modelling was used to compare the pre- and post-course test scores. The pairings of pre- and post-course scores were not known because of a confidentiality clause.
Results.
Of the 120 delegates, 71 (59%) took the pre-course test and 120 (100%) took the post-course test. The median score improved significantly from 2 (interquartile range IQR, 0.5–3.5) to 6 (IQR, 4.5– 7.5) bootstrap p<0.0001 for every single one of the randomly allocated pairings. Most delegates had poor cognitive skills for the UKA before the course and improved significantly after the course. Subanalysis of each question topic showed significant improvement in scores for all topics after the course (bootstrap p<0.0001). Nonetheless, the extent to which individual topic scores improved varied widely. The odds ratio for the preversus post-course total test score was 4.36.
Conclusion.
A mixed continuing medical education course could enhance the non-technical (cognitive) skills for UKA.
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