The form of the species richness-productivity relationship (SRPR) is both theoretically important and contentious. In an effort to distill general patterns, ecologists have undertaken meta-analyses, within which each SRPR data set is first classified into one of five alternative forms: positive, humped (unimodal), negative, U-shaped (unimodal), and no relationship. Herein, I first provide a critique of this approach, based on 68 plant data sets/studies used in three meta-analyses published in Ecology. The meta-analyses are shown to have resulted in highly divergent outcomes, inconsistent and often highly inappropriate classification of data sets, and the introduction and multiplication of errors from one meta-analysis to the next. I therefore call on the ecological community at large to adopt a far more rigorous and critical attitude to the use of meta-analysis. Second, I develop the argument that the literature on the SRPR continues to be bedeviled by a common failing to appreciate the fundamental importance of the scale of analysis, beginning with the confusion evident between concepts of grain, focus, and extent. I postulate that variation in the form of the SRPR at fine scales of analysis owes much to artifacts of the sampling regime adopted. An improved understanding may emerge from combining sampling theory with an understanding of the factors controlling the form of species abundance distributions and species accumulation curves.
Motivation: Prior biological knowledge greatly facilitates the meaningful interpretation of gene-expression data. Causal networks constructed from individual relationships curated from the literature are particularly suited for this task, since they create mechanistic hypotheses that explain the expression changes observed in datasets. Results: We present and discuss a suite of algorithms and tools for inferring and scoring regulator networks upstream of gene-expression data based on a large-scale causal network derived from the Ingenuity Knowledge Base. We extend the method to predict downstream effects on biological functions and diseases and demonstrate the validity of our approach by applying it to example datasets.
In the third Joint Danube Survey (JDS3), emerging organic contaminants were analysed in the dissolved water phase of samples from the Danube River and its major tributaries. Analyses were performed using solid-phase extraction (SPE) followed by ultra-high-pressure liquid chromatography triple-quadrupole mass spectrometry (UHPLC-MS-MS) and gas chromatography–mass spectrometry (GC–MS). The polar organic compounds analysed by UHPLC-MS-MS were 1H-benzotriazole, methylbenzotriazoles, carbamazepine, 10,11-dihydro-10,11-dihydroxy-carbamazepine, diclofenac, sulfamethox-azole, 2,4-D (2,4-dichlorophenoxyacetic acid), MCPA (2-methyl-4-chlorophenoxyacetic acid), metolachlor, cybutryne (irgarol), terbutryn, DEET ( , -diethyl- -toluamide), and several perfluoroalkyl acids (C –C ; C = perfluorooctanoic acid (PFOA)) and perfluorooctansulfonic acid (PFOS). In addition, several organophosphorus flame retardants were analysed by GC-MS. The most relevant compounds identified in the 71 water samples, in terms of highest median and maximum concentrations, were 1H-benzotriazole, tris(1-chloro-2-propyl)phosphate (TCPP), methylbenzotriazoles, carbama-zepine and its metabolite, DEET, sulfamethoxazole, tris(isobutyl)phosphate (TiBP), tris(2-chloroethyl)phosphate (TCEP), PFOA, PFOS and diclofenac. The concentrations of these compounds in the samples were generally below the environmental quality standard (EQS) threshold values, with the exception of PFOS, the concentration of which exceeded the annual average water EQS limit of 0.65 ng/L along the whole river, and also exceeded the fish biota EQS of 9.1 μg/kg. In addition, the proposed EQS for diclofenac, of 0.1 μg/L, was exceeded in the Arges River in Romania (255 ng/L).
The pathogenesis of infection in tilapia has not been fully described. To understand this, we investigated the clinic-pathological features of acute experimental septicemia in tilapia ( ) after receiving an intra-peritoneal injection with THN-1901GFP. Immunohistochemistry and sections of pathological tissues were used to estimate the level of damage in the head-kidney, liver, spleen and trunk-kidney. The expression of FasL was analyzed by western blotting in these samples based on their damage levels. Leucocytes were isolated from the head-kidney and incubated with THN-1901GFP. Then, phagocytosis, programmed cell death and the expression of FasL were analyzed. The infected tissues showed varying degrees of necrosis and histolysis. The serous membrane of the intestine was dissolved by THN-1901GFP. Antigens of THN-1901GFP accumulated in different parts of the infected organs. In the head-kidney and spleen, the expression of FasL was up-regulated in parallel with increased tissue damage. After being incubated with THN-1901GFP, the phagocytic capacity and ability were both very high and the expression of FasL remained high in leucocytes. THN-1901GFP was able to survive for a long period of time after being engulfed by phagocytic cells. These findings offer insight into the pathogenesis of infection in tilapia.
The program Fluctuation AnaLysis CalculatOR (FALCOR) is a web tool designed for use with Luria-Delbrück fluctuation analysis to calculate the frequency and rate from various mutation assays in bacteria and yeast. Three calculation methods are available through this program: (i) Ma-Sandri-Sarkar Maximum Likelihood Estimator (MSS-MLE) method, (ii) Lea-Coulson method of the median (LC) and (iii) frequency. Availability: The FALCOR rate calculator is currently accessible at http://www.mitochondria.org/protocols/FALCOR.html. This program is written as a Java™ Applet, requiring a web browser enabled with Sun MicroSystems' Java Virtual Machine. Contact: email@example.com
Binding of dsDNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) triggers formation of the metazoan second messenger c[G(2′,5′)pA(3′,5′)p], which binds the signaling protein STING with subsequent activation of the interferon (IFN) pathway. We show that human hSTING adopts a “closed” conformation upon binding c[G(2′,5′)pA(3′,5′)p] and its linkage isomer c[G(2′,5′)pA(2′,5′)p], as does mouse mSting on binding c[G(2′,5′)pA(3′,5′)p], c[G(3′,5′)pA(3′,5′)p] and the antiviral agent DMXAA, leading to similar “closed” conformations. Comparing hSTING to mSting, 2′,5′-linkage-containing cGAMP isomers were more specific triggers of the IFN pathway compared to the all-3′,5′-linkage isomer. Guided by structural information, we identified a unique point mutation (S162A) placed within the cyclic-dinucleotide-binding site of hSTING that rendered it sensitive to the otherwise mouse-specific drug DMXAA, a conclusion validated by binding studies. Our structural and functional analysis highlights the unexpected versatility of STING in the recognition of natural and synthetic ligands within a small-molecule pocket created by the dimerization of STING. 2′,5′-linkage-containing cGAMP second messengers bind to human and mouse STING with stronger affinity than 3′,5′ isomers to trigger interferon signaling. A point mutation in human STING may explain the lack of sensitivity to DMXAA, a drug with potent antiviral and antitumorigenic effects in mice.
Because formaldehyde is toxic and creates cross-links that may hinder immunohistochemical studies, we tested 3 new cross-linking (F-Solv [Adamas, Rhenen, the Netherlands]) and non cross-linking (FineFIX [Milestone, Bergamo, Italy] and RCL2 [Alphelys, Plaisir, France]) alcohol-based fixatives for routine staining in comparison with neutral buffered formalin (NBF) as the "gold standard" Fresh tissue samples were divided into 4 equal pieces and fixed in all fixatives for varying times. After paraffin embedding, H&E staining, 7 common histochemical stains, and 9 common immunohistochemical stains were performed. RCL2 fixation resulted in soft and slippery tissue, causing sectioning difficulties. F-Solv and FineFIX led to partial tissue disintegration during fixation. F-Solv performed morphologically similar to NBF but needed considerable protocol adjustments before being applicable in daily histologic and immunohistochemical practice. FineFiX did not necessitate major protocol changes but caused shrinkage artifacts, degranulation, and lysis of RBCs. RCL2 generated morphologically overall good results without major protocol changes but caused pigment deposition, degranulation, and RBC lysis. The alcohol-based fixatives had positive and negative attributes and environmental drawbacks, and none was overall comparable to NBF with regard to macroscopy, morphologic evaluation, and immunohistochemical studies.
Abstract In order to mitigate the effect of non-stationarity in frequency domain analysis of data, we propose a modification to the power spectral estimation, a widely used technique to characterize physiological signals. Spectral analysis requires partitioning data into smaller epochs determined by the desired frequency resolution. The modified approach proposed here involves dividing the data within each epoch by the standard deviation of the data for that epoch. We applied this modified approach to cardiac beat-to-beat interval data recorded from a newborn infant undergoing hypothermia treatment for birth asphyxia. The critically ill infant had episodes of tachyarrhythmia, distributed sporadically throughout the study, which affected the stationarity of the heart rate. Over the period of continuous heart rate recording, the infant's clinical course deteriorated progressively culminating in death. Coinciding with this clinical deterioration, the heart rate signal showed striking changes in both low-frequency and high-frequency power indicating significant impairment of the autonomic nervous system. The standard spectral approach failed to capture these phenomena because of the non-stationarity of the signal. Conversely, the modified approach proposed here captured the deteriorating physiology of the infant clearly.
A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC–MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm−2) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy. Figure Wipe sampling procedure for the determination of cytotoxic drugs
1. Senescence is usually viewed as increased age-specific mortality or decreased age-specific fecundity due to the declining ability of natural selection to remove deleterious age-specific mutations with age. In herbaceous perennial plants, trends in age-specific mortality are often confounded by size. Age-indeterminate senescence, where accumulated physiological damage varies strongly with environment, may be a better model of senescence in these species. 2. We analysed trends in size and fertility in Plantago lanceolata, using a long-term demographic census involving > 10 years and > 8000 individuals in four cohorts. We used elasticity and pairwise invasion analysis of life-history function parameterized age × stage matrices to assess whether the force of natural selection declined with age. Then, we used reverse age analysis of size and fertility to assess whether age-indeterminate senescence occurred. Reverse age analysis uses longitudinal data for individuals that have died to look at trait patterns as a function of both age and remaining time to death. We hypothesized that (i) the strength of natural selection would decline strongly with age, and (ii) physiological condition would deteriorate for several years prior to death. 3. Both elasticity and invasion analyses suggested that the strength of natural selection through mortality declined strongly with age once size was accounted for. Further, reverse age analyses showed that individuals shrank for 3 years prior to death, suggesting physiological decline. Inflorescence production declined with age, and also declined in the 3 years prior to death regardless of overall age. 4. Synthesis. The hypothesis that plants escape senescence generally assumes that plants can continue to grow larger and increase reproduction as they get older. The results here show that size and reproduction decline with age and the rates of these declines towards death are life span- and age dependent. Further research is needed to delineate the importance of age-determinate vs. age-indeterminate factors in senescence patterns across species.