The hypotheses that beta diversity should increase with decreasing latitude and increase with spatial extent of a region have rarely been tested based on a comparative analysis of multiple datasets, ...and no such study has focused on stream insects. We first assessed how well variability in beta diversity of stream insect metacommunities is predicted by insect group, latitude, spatial extent, altitudinal range, and dataset properties across multiple drainage basins throughout the world. Second, we assessed the relative roles of environmental and spatial factors in driving variation in assemblage composition within each drainage basin. Our analyses were based on a dataset of 95 stream insect metacommunities from 31 drainage basins distributed around the world. We used dissimilarity‐based indices to quantify beta diversity for each metacommunity and, subsequently, regressed beta diversity on insect group, latitude, spatial extent, altitudinal range, and dataset properties (e.g., number of sites and percentage of presences). Within each metacommunity, we used a combination of spatial eigenfunction analyses and partial redundancy analysis to partition variation in assemblage structure into environmental, shared, spatial, and unexplained fractions. We found that dataset properties were more important predictors of beta diversity than ecological and geographical factors across multiple drainage basins. In the within‐basin analyses, environmental and spatial variables were generally poor predictors of variation in assemblage composition. Our results revealed deviation from general biodiversity patterns because beta diversity did not show the expected decreasing trend with latitude. Our results also call for reconsideration of just how predictable stream assemblages are along ecological gradients, with implications for environmental assessment and conservation decisions. Our findings may also be applicable to other dynamic systems where predictability is low.
Beta diversity should vary along major ecological gradients. We used data for 95 stream insect metacommunities to examine if beta diversity showed general patterns over the world. We did not find clear patterns along latitudinal, altitudinal or environmental gradients, suggesting that stochasticity typical of frequently‐disturbed stream ecosystems may hinder finding clear patterns in stream insect beta diversity.
Summary Background Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3–9 h after the onset of the symptoms of stroke in patients with ...presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI). Methods In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (1:1:1) to 90 μg/kg desmoteplase, 125 μg/kg desmoteplase, or placebo within 3–9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0–2 points, and a Barthel index of 75–100. Secondary endpoints included change in lesion volume between baseline and day 30, rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , NCT00111852. Findings Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 μg/kg desmoteplase; 66 received 125 μg/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6–14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10·6 cm3 and 52·5 cm3 , respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 μg/kg desmoteplase, 36% (24 of 66) for 125 μg/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 μg/kg desmoteplase 14·0% (0·5 cm3 ); 125 μg/kg desmoteplase 10·8% (0·3 cm3 ); placebo −10·0% (−0·9 cm3 ). The rates of symptomatic intracranial haemorrhage were 3·5% (2 of 57) for 90 μg/kg desmoteplase, 4·5% (3 of 66) for 125 μg/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% 3 of 57 for 90 μg/kg desmoteplase; 21% 14 of 66 for 125 μg/kg desmoteplase; and 6% 4 of 63 for placebo). Interpretation The DIAS-2 study did not show a benefit of desmoteplase given 3–9 h after the onset of stroke. The high response rate in the placebo group could be explained by the mild strokes recorded (low baseline NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase. Funding PAION Deutschland GmbH; Forest Laboratories.
Fbxo7 is the substrate-recognition subunit of an SCF-type ubiquitin E3 ligase complex. It has physiologically important functions in regulating mitophagy, proteasome activity and the cell cycle in ...multiple cell types, like neurons, lymphocytes and erythrocytes. Here, we show that in addition to the previously known Parkinsonian and hematopoietic phenotypes, male mice with reduced Fbxo7 expression are sterile. In these males, despite successful meiosis, nuclear elongation and eviction of histones from chromatin, the developing spermatids are phagocytosed by Sertoli cells during late spermiogenesis, as the spermatids undergo cytoplasmic remodeling. Surprisingly, despite the loss of all germ cells, there was no evidence of the symplast formation and cell sloughing that is typically associated with spermatid death in other mouse sterility models, suggesting that novel cell death and/or cell disposal mechanisms may be engaged in Fbxo7 mutant males. Mutation of the
Drosophila
Fbxo7 ortholog,
nutcracker
(
ntc
) also leads to sterility with germ cell death during cytoplasmic remodeling, indicating that the requirement for Fbxo7 at this stage is conserved. The
ntc
phenotype was attributed to decreased levels of the proteasome regulator, DmPI31 and reduced proteasome activity. Consistent with the fly model, we observe a reduction in PI31 levels in mutant mice; however, there is no alteration in proteasome activity in whole mouse testes. Our results are consistent with findings that Fbxo7 regulates PI31 protein levels, and indicates that a defect at the late stages of spermiogenesis, possibly due to faulty spatial dynamics of proteasomes during cytoplasmic remodeling, may underlie the fertility phenotype in mice.
Flow-metabolism coupling is thought to be deranged after traumatic brain injury, while the effects of propofol on flow-metabolism coupling are controversial. We have used a step increase in target ...plasma propofol concentration in head injured patients to explore flow-metabolism coupling in these patients.
Ten patients with a moderate to severe head injury received a step increase in propofol target controlled infusion of 2 μg ml−1. Cerebral tissue gas measurements were recorded using a multimodal sensor, and regional chemistry was assessed using microdialysis. Arterial-jugular venous oxygen differences (AVDO2) were measured and all patients had cortical function monitoring (EEG).
The step increase in propofol led to a large increase in EEG burst-suppression ratio (0% (range 0–1.1) to 46.1% (range 0–61.7), P<0.05); however, this did not significantly change tissue gas levels, tissue chemistry, or AVDO2.
Flow-metabolism coupling remains intact during a step increase in propofol after traumatic brain injury. The EEG burst-suppression induced by propofol after traumatic brain injury does not appear to be a useful therapeutic tool in reducing the level of regional ischaemic burden.
A series of novel 8‐aryl‐2‐morpholino quinazolines (11a–n, 12a–d, 14a–f, and 15) were synthesized from the precursor 2‐thioxo quinazolin‐4‐ones 8. The 8‐aryl‐2‐morpholino quinazolines compounds were ...assayed for DNA‐PK and PI3K. All compounds showed low DNA‐PK % inhibition activity at 10 μM compound concertation, and the most active was 8‐(dibenzob,dthiophen‐4‐yl) 12d with 38% inhibition. Similar pattern of PI3K α, β, γ, and δ isoforms inhibition activity at 10 μM were observed. The most active isoform was PI3K δ of 41% inhibition for 8‐(dibenzob,dfuran‐4‐yl) compound 11. Most compounds were less active than expected in spite of the strong structural resemblance to known inhibitors (NU7441, 3, 4, and 6). Loss of activity could be attributed to the tautomerization to the aromatic enol (4‐OH), which could specify that the important functional group for the activity is the 4‐carbonyl (C=O) group. Alternatively, the aromatization of the pyrimidine heterocyclic ring could alter the conformation, and thus binding site, of the 2‐morpholine ring, which could reduce the compound‐receptor hydrogen bonding to the morpholine 4‐oxygen. Selected compounds displayed appreciable cytotoxicity with 6‐chloro‐8‐(dibenzob,dthiophen‐4‐yl)‐2‐morpholinoquinazolin‐4(1H)‐one 11j exhibiting the greatest activity with an IC50 of 9.95 μM. Therefore, the mechanism of the cytotoxicity of compound 11j were not through DNA‐PK or PI3K inhibition activity.
Coumarin, a naturally occurring or synthesised phytochemical, displays a wide range of biological activities. However, chromen-2-ones fused with 1,3-benzoxazine rings is not well documented and there ...is a gap in the literature which required engaging. The substituted-2-thioxo-chromen-oxazine linear compounds 14a-i and angular compounds 16a-e were synthesised from the reaction of hydroxy-substituted-chromene-carboxylic 10-13 with freshly prepared Ph
3
P(SCN)
2
. 2-Morpholino-substituted-chromen-oxazine-4,8-dione and 8-morpholino-substituted-chromen-oxazine-2,10-dione 15a-f and 17 were synthesised from the reaction of the corresponding oxazines 14 and 16 with morpholine. PI3K activity was observed for the hydroxy-substituted-chromene-carboxylic acid of which compound 13b showed moderate PI3Kγ (IC
50
=
5.56 μM) and PI3Kα (IC
50
=
14.7 μM) activity. Additionally, 8-morpholino-chromen-oxazine-2,10-dione 17a showed isoform selective PI3Kδ activity with IC
50
=
5.08 μM with non-DNA-PK ≥ 100 μM. Consequently compound 17a can be considered as a selective PI3Kδ inhibitor with non-DNA-PK at compound concentrations ≥100 μM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A number of new 2-(pyridin-3-ylamino)-4H-(substituted) benze-1,3-oxazin-4-ones were synthesized 10a–g. These were then reacted with the hydro-halogen salt of 2, 3 and 4-(halo-methyl) pyridine in the ...presence of Cs2CO3 to give eighteen new 2-(N-substituted (pyridin-3-ylmethyl) amino)-substituted-1,3-benzoxazines (compounds 11a–i, 13a–c, and 15a–f). X-ray crystallography was used to confirm that the 2-N-substituted structures 11 and 13 were formed rather than the 3-N-substitution analogues 12 and 14. Eleven of the new compounds were tested for their effect on collagen induced platelet aggregation and it was found that the most active inhibitory compound was 8-methyl-2-(pyridin-3-yl(pyridin-3-ylmethyl)amino)-7-(pyridin-3-ylmethoxy)-4H-benze-1,3-oxazin-4-one 15e with an IC50 of 10 ± 2 μM. DNA-dependent protein kinase (DNA-PK) inhibition data for 12 previously prepared 2-morpholino substituted-1,3-benzoxazines (compounds 19–31) were measured and showed high to moderate activity where the most active compound was compound 27 with an IC50 of 0.28 μM. Furthermore DNA-PK inhibition data for six newly prepared 2-(N-substituted (pyridin-3-ylmethyl) amino)-substituted-1,3-benzoxazines (compounds 11b, 13a–b, 15a–b and 15e) and 8-methyl-7-(pyridin-3-ylmethoxy)-3-(pyridin-3-ylmethyl)-2H-benze-1,3-oxazin-2,4(3H)-dione 17d were measured and moderate to low inhibitory activity was observed, with the most active of the compounds in this series being 8-methyl-2-(pyridin-3-yl(pyridin-3-ylmethyl)amino)-7-(pyridin-3-ylmethoxy)-4H-benze-1,3-oxazin-4-one 15e with an IC50 of 2.5 μM. PI3K inhibition studies revealed that compound 27 is highly potent (IC50 for PI3Kα = 0.13 μM, PI3Kβ = 0.14 μM, PI3Kγ = 0.72 μM, PI3Kδ = 2.02 μM). Compound 22 with 7-2-(4-methylpiperazin-1-yl)ethoxy group shows greater inhibition of DNA-PK over PI3K.
Docking of some 2-morpholino-substituted-1,3-benzoxazine compounds 19–31 within the binding pocket and structure–activity relationships (SAR) analyses were performed with results agreeing well with observed activities.
DNA-PK and PI3K inhibition data of 2-morpholino substituted-1,3-benzoxazines and 2-(N-substituted (pyridin-3-ylmethyl)amino)-substituted-1,3-benzoxazines compounds were measured and showed high to moderate activity. Display omitted
► Synthesis of novel 2-amino-substituted-1,3-benzoxazines. ► DNA-PK inhibition data for 2-amino-substituted-1,3-benzoxazines. ► 2-(Pyridin-3-ylmethyl)-1,3-benzoxazines showed significant DNA-PK inhibition. ► PI3K inhibition studies revealed that compound 27 is highly potent. ► Docking and SAR study for some of the 2-morpholino-1,3-benzoxazines.
Abstract The experiment was tried in the western region of Iraq and aims to study the effects of using conservation agriculture applications in the water properties of Gypsiferous - desert soil. The ...study area was divided into three blocks. In each block four treatments were randomly distributed: Tillage with Covering T.C Tillage without Covering T.NC No-Tillage with Covering NT.C and No-Tillage without Covering NT.NC. The experiment was designed by using a Randomize Completely Block Design (RCBD) by 2 tillage methods 2 mulching and 3 replicates so the sum was 12 experimental units. Units were planted in two agricultural seasons Barley crop in winter and Mung bean in summer season. There was a significant effect of the interaction between coverage and the measurement stage on the mean of cumulative infiltration as its value over 1 hour at the coverage treatment in the S2 stage (between the two seasons) reached 12.53 cm. The highest mean of cumulative infiltration in the NT.C was (8.43 cm) with a non-significant difference from the lowest average (5.94) in the T.NC. As for the average unsaturated hydraulic conductivity (Kns) it did not differ from the results of the cumulative infiltration in terms of being the highest and lowest treatment as the range is 1.46 cm. hr −1 at T.NC and 2.09 cm. hr −1 at NT.C the hydraulic conductivity rating for all treatments was (moderately high). The NT.C treatment also gave the highest mean long-term cumulative infiltration and infiltration rate with greater uniformity of moisture distribution between the soil layers.
OBJECTIVES
Although the association between chronic obstructive pulmonary disease (COPD) and adverse surgical outcomes has been previously demonstrated, the impact of COPD severity on postoperative ...mortality and morbidity remains unclear. Our objective was to analyse the prognostic implication of COPD stages as defined by the Global Initiative for Chronic Obstructive Lung Disease.
METHODS
Between September 1997 and April 2010, 13 638 patients undergoing first time isolated CABG were retrospectively reviewed, of whom 2421 patients were excluded due to lack of spirometry records or restrictive pattern on spirometry. The remaining 11 217 patients were divided into three groups: group 1 (including patients with normal spirometry and patients with mild COPD (FEV1/FVC ratio < 70%, FEV1 ≥ 80% predicted), group 2 (moderate COPD: FEV1/FVC ratio < 70%, 50% ≤ FEV1 < 80% predicted) and group 3 (severe COPD: FEV1/FVC ratio < 70%, FEV1 < 50% predicted). Logistic regression was used to examine the effect of COPD severity on early mortality and morbidity, after adjusting for differences in patient characteristics.
RESULTS
Early mortality in the three groups was 1.4, 2.9 and 5.7% respectively (P < 0.001). Similarly, a consistent trend of increasing frequency of postoperative complications with advanced COPD stage was noted. On multivariate analysis, severe COPD was found to be significantly associated with early mortality adjusted OR, 2.31 (95% CI) (1.23-4.36), P = 0.01.
CONCLUSIONS
The severity of COPD as defined by spirometry can be a prognostic marker in patients undergoing CABG. Spirometric criteria may help refining currently used operative risk scores.
BACKGROUND The time spent on diverse social, physical, and educational activities among healthcare undergraduates (HCUs) tremendously impacts their academic and personal lives. Therefore, this study ...aimed to assess the social, physical, and educational activities among HCUs at King Saud University (KSU) in Riyadh, Saudi Arabia (SA). MATERIAL AND METHODS A cross-sectional, self-prepared, and pre-tested e-questionnaire (electronic questionnaire) based study using a convenience sampling design in a university in SA from August 21 to November 21, 2023 was conducted to assess their various activities outside of classes, using a 16-item e-questionnaire to investigate time spent on social (4 items), physical (3 items), and educational activities (3 items). RESULTS A total of 452 HCUs completed the e-questionnaires, giving a response rate of 92.62%. Of them, 50.45% were females, the median age was 23 years, and 32.08% (n=145) were medical undergraduates. About 57% of the HCUs spent 1-2 h per day on educational activities during the day, while 32.7% of the HCUs spent 2 h per day on social media, and 62.6% spent 3-4 h per day with family. The findings revealed that the 140 females spent significantly more time (1-2 h) reading and writing compared to the 117 male HCUs (P=0.001). Age was found to be associated with time spent on education by HCUs (P=0.001). CONCLUSIONS Our findings among HCUs show that most spend a significant amount of time on educational activities during the day. Undergraduates also spend time with their families and participate in other social activities.
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