Relationships between fish feeding guild and trophic structure in English lowland shallow lakes subject to anthropogenic influence: implications for lake restoration

The shallow lakes of Eastern England have been subject to intense anthropogenic pressures including nutrient enrichment and fish stocking. We sought to determine the relationships between fish community structure and other ecosystem characteristics in 28 of these lakes through classification of fish species into piscivorous, zooplanktivorous and benthivorous feeding guilds according to the literature. Canonical correspondence analysis produced clear associations between fish and ecosystem characteristics that generally agreed with other theoretical (e.g. the alternative stable states hypothesis) and empirical studies, but with some important differences. There was a striking lack of relationships between nutrients and other variables, indicating the importance of top-down rather than bottom-up processes as a structuring force in the generally eutrophic study lakes. The presence of submerged (and shoreline) vegetation was associated with a diverse assemblage of apparently co-existing piscivorous (principally pike Esox lucius) and zooplanktivorous species. Perch Perca fluviatilis, a significant predator in other studies, was unimportant and argued to be limited by water quality in the extremely shallow lakes. In contrast, the benthivorous fish guild (principally carp Cyprinus carpio, bream Abramis brama and tench Tinca tinca) essentially represented the inverse of the potential pelagic associations between piscivores/zooplanktivores and vegetation. The introduction of large benthivores to many study lakes could have precipitated a loss of submerged vegetation through direct uprooting during foraging, with the effect of simplifying the fish community being most acute where littoral vegetation was limited by other anthropogenic factors. It is implied that attempts to promote or restore submerged vegetation in these lakes would best target benthivorous species.     

Effects of i and i+3 residue identity on cis-trans isomerism of the aromatic(i+1)-prolyl(i+2) amide bond: implications for type VI beta-turn formation

Cis-trans isomerization of amide bonds plays critical roles in protein molecular recognition, protein folding, protein misfolding, and disease. Aromatic-proline sequences are particularly prone to exhibit cis amide bonds. The roles of residues adjacent to a tyrosine-proline residue pair on cis-trans isomerism were examined. A short series of peptides XYPZ was synthesized and cis-trans isomerism was analyzed. Based on these initial studies, a series of peptides XYPN, X = all 20 canonical amino acids, was synthesized and analyzed by NMR for i residue effects on cis-trans isomerization. The following effects were observed: (a) aromatic residues immediately preceding Tyr-Pro disfavor cis amide bonds, with K(trans/cis)= 5.7-8.0, W > Y > F; (b) proline residues preceding Tyr-Pro lead to multiple species, exhibiting cis-trans isomerization of either or both X-Pro amide bonds; and (c) other residues exhibit similar values of K(trans/cis) (= 2.9-4.2), with Thr and protonated His exhibiting the highest fraction cis. beta-Branched and short polar residues were somewhat more favorable in stabilizing the cis conformation. Phosphorylation of serine at the i position modestly increases the stability of the cis conformer. In addition, the effect of the i+3 residue was examined in a limited series of peptides TYPZ. NMR data indicated that aromatic residues, Pro, Asn, Ala, and Val at the i+3 residue all favor cis amide bonds, with aromatic residues and Asn favoring more compact phi at Tyr(cis) and Ala and Pro favoring more extended phi at Tyr(cis). D-Alanine at the i+3 position particularly disfavors cis amide bonds.     

Triaminotriazine DNA helicase inhibitors with antibacterial activity

Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB helicase provided a triaminotriazine inhibitor with good antibacterial activity but associated cytotoxicity toward mammalian cells. Synthesis of analogs provided a few inhibitors that retained antibacterial activity and demonstrated a significant reduction in cytotoxicity. The impact of serum and initial investigations toward a mode of action highlight several features of this class of compounds as antibacterials.     

Laser scanning cytometry in human brain slices.

BACKGROUND: The Laser Scanning Cytometry (LSC) offers quantitative fluorescence analysis of cell suspensions and tissue sections. METHODS: We adapted this technique to immunohistochemical labelled human brain slices. RESULTS: We were able to identify neurons according to their labelling and to display morphological structures such as the lamination of the entorhinal cortex. Further, we were able to distinguish between neurons with and without cyclin B1 expression and we could assign the expression of cyclin B1 to the cell islands of layer II and the pyramidal neurons of layer V of the entorhinal cortex in Alzheimer's disease effected brain. In addition, we developed a method depicting the three-dimensional distribution of the cells in intact tissue sections. CONCLUSIONS: In this pilot experiments we could demonstrate the power of the LSC for the analysis of human brain sections.     

Myocardial contractile function during postischemic low-flow reperfusion: critical thresholds of NADH and O2 delivery

The degree of myocardial oxygen delivery (Do2) that is necessary to reestablish functional contractile activity after short-term global ischemia in heart is not known. To determine the relationship between Do2 and recovery of contractile and metabolic functions, we used tissue NADH fluorometric changes to characterize adequacy of reperfusion flow. Isolated perfused rat hearts were subjected to global ischemia and were reperfused at variable flow rates that ranged from 1 to 100% of baseline flow. Myocardial function and tissue NADH changes were continuously measured. NADH fluorescence rapidly increased and plateaued during ischemia. A strong inverse logarithmic correlation between NADH fluorescence and reperfusion Do2 was demonstrated (r = -0.952). Left ventricular function (rate-pressure product) was inversely related to NADH fluorescence at reperfusion flows from 25 to 100% of baseline (r = -0.922) but not at lower reperfusion flow levels. An apparent reperfusion threshold of 25% of baseline Do2 was necessary to resume contractile function. At very low reperfusion flows (1% of baseline), another threshold flow was identified at which NADH levels increased beyond that observed during global ischemia (3.4 +/- 3.0%, means +/- SE, n = 9), which suggests further reduction of the cellular redox state. This NADH increase at 1% of baseline reperfusion flow was blocked by removing glucose from the perfusate. NADH fluorescence is a sensitive indicator of myocardial cellular oxygen utilization over a wide range of reperfusion Do2 values. Although oxygen is utilized at very low flow rates, as indicated by changes in NADH, a critical threshold of approximately 25% of baseline Do2 is necessary to restore contractile function after short-term global ischemia.     

In vitro induction of neoantigen-specific T cells in myelodysplastic syndrome,a disease with low mutational burden

Therapies that utilize immune checkpoint inhibition work by leveraging mutation-derived neoantigens and have shown greater clinical efficacy in tumors with higher mutational burden. Whether tumors with a low mutational burden are susceptible to neoantigen-targeted therapy has not been fully addressed. To examine the feasibility of neoantigen-specific adoptive T-cell therapy, the authors studied the T-cell response against somatic variants in five patients with myelodysplastic syndrome (MDS), a malignancy with a very low tumor mutational burden. DNA and RNA from tumor (CD34⁺) and normal (CD3⁺) cells isolated from the patients’ blood were sequenced to predict patient-specific MDS neopeptides. Neopeptides representing the somatic variants were used to induce and expand autologous T cells ex vivo, and these were systematically tested in killing assays to determine the proportion of neopeptides yielding neoantigen-specific T cells. The authors identified a total of 32 somatic variants (four to eight per patient) and found that 21 (66%) induced a peptide-specific T-cell response and 19 (59%) induced a T-cell response capable of killing autologous tumor cells. Of the 32 somatic variants, 11 (34%) induced a CD4⁺ response and 11 (34%) induced a CD8⁺ response that killed the tumor. These results indicate that in vitro induction of neoantigen-specific T cells is feasible for tumors with very low mutational burden and that this approach warrants investigation as a therapeutic option for such patients.     

Retrospective study of the parental origin of the extra chromosome in trisomy 18 (Edwards syndrome)

The parental origin of the extra chromosome in trisomy 18 was traced in 30 informative families using highly polymorphic (CA) repeats mapped on the long arm of chromosome 18. Proband DNA was recovered from slides of chromosome preparations in 28 cases and from paraffin-embedded tissues in two cases. The extra chromosome was found to be of maternal origin in 26 cases (86.7%), and paternal origin in 4 cases (13.3%).     

Pregnancy does not affect HIV incidence test results obtained using the BED capture enzyme immunoassay or an antibody avidity assay

Background

Accurate incidence estimates are needed for surveillance of the HIV epidemic. HIV surveillance occurs at maternal-child health clinics, but it is not known if pregnancy affects HIV incidence testing.

Methods

We used the BED capture immunoassay (BED) and an antibody avidity assay to test longitudinal samples from 51 HIV-infected Ugandan women infected with subtype A, C, D and intersubtype recombinant HIV who were enrolled in the HIVNET 012 trial (37 baseline samples collected near the time of delivery and 135 follow-up samples collected 3, 4 or 5 years later). Nineteen of 51 women were also pregnant at the time of one or more of the follow-up visits. The BED assay was performed according to the manufacturer''s instructions. The avidity assay was performed using a Genetic Systems HIV-1/HIV-2 + O EIA using 0.1M diethylamine as the chaotropic agent.

Results

During the HIVNET 012 follow-up study, there was no difference in normalized optical density values (OD-n) obtained with the BED assay or in the avidity test results (%) when women were pregnant (n = 20 results) compared to those obtained when women were not pregnant (n = 115; for BED: p = 0.9, generalized estimating equations model; for avidity: p = 0.7, Wilcoxon rank sum). In addition, BED and avidity results were almost exactly the same in longitudinal samples from the 18 women who were pregnant at only one study visit during the follow-up study (p = 0.6, paired t-test).

Conclusions

These results from 51 Ugandan women suggest that any changes in the antibody response to HIV infection that occur during pregnancy are not sufficient to alter results obtained with the BED and avidity assays. Confirmation with larger studies and with other HIV subtypes is needed.