Tabernacle Butte

33 p. : ill. ; 24 cm.Includes bibliographical references (p. 29-33)

Bioaccumulation of Polychlorinated Biphenyls (PCBs) in Atlantic Sea Bream (Archosargus rhomboidalis) from Kingston Harbour, Jamaica

Multiple sizes of Sea bream were collected from Kingston Harbour, Jamaica, to assess steady state bioaccumulation of polychlorinated biphenyls (PCBs) in a tropical fish. Sea beam fork lengths ranged from 7.3-21.5 cm (n=36 fish) and tissue lipids decreased with body length. Larger fish had lower δ13C isotopes compared to smaller fish, suggesting a change in diet. Linear regressions showed no differences in lipid equivalent sum PCB concentrations with size. However, differences in individual congener bioaccumulation trajectories occurred. Less hydrophobic PCBs decreased with increasing body length, intermediate PCBs showed no trend, whereas highly hydrophobic (above log KOW of 6.5) PCBs increased. The different congener patterns were interpreted to be a result of decreases in overall diet PCB concentrations with increased fish length coupled with differences in PCB toxicokinetics as a function of hydrophobicity yielding dilution, pseudo-steady state and non-steady state bioaccumulation patterns

Behavioural interactions between co‐habiting females and their impact on productivity and offspring sex ratios in the coffee berry borer, Hypothenemus hampei

The coffee berry borer (CBB) Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae) has invaded all coffee-producing regions of the world and causes substantial economic losses every year. A single female beetle typically infests one coffee berry, which her offspring consume over the course of development. Offspring then engage in sib-mating before daughters fly off to infest new berries. We assessed infestation rates across different locations in Jamaica and found a strong positive correlation between double infestation and overall infestation rate, suggesting that females prefer to breed alone but will tolerate sharing a berry under resource constraints. Using an artificial habitat to study productivity and behaviour in the laboratory, we found that single females produced significantly more offspring per capita than two females, suggesting that co-habitation is costly. Accordingly, co-habiting females spent a significant proportion of their time engaged in antagonistic interactive behaviours such as pushing. When daughter beetles were given the opportunity to stay with their mothers or to infest a new berry, they tended to leave. In contrast to some related beetle species, which exhibit gregariousness and even cooperative behaviour, beneficial social interactions in the CBB appear to be limited to parental care

Antagonists of Calcium Fluxes and Calmodulin Block Activation of the p21-Activated Protein Kinases in Neutrophils

Neutrophils stimulated with fMLP or a variety of other chemoattractants that bind to serpentine receptors coupled to heterotrimeric G proteins exhibit rapid activation of two p21-activated protein kinases (Paks) with molecular masses of ~63 and 69 kDa (y- and a-Pak). Previous studies have shown that products of phosphatidylinositol 3-kinase and tyrosine kinases are required for the activation of Paks. We now report that a variety of structurally distinct compounds which interrupt different stages in calcium/calmodulin (CaM) signaling block activation of the 63- and 69-kDa Paks in fMLP-stimulated neutrophils. These antagonists included selective inhibitors of phospholipase C (1-[6-((17ß-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole- 2,5-dione), the intracellular Ca^(2+) channel (8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate), CaM (N-(6-aminohexyl)-5- chloro-1-naphthalenesulfonamide; N-(4-aminobutyl)-5-chloro-1-naphthalenesulfonamide; trifluoperazine), and CaM-activated protein kinases (N-[2-(N-(chlorocinnamyl)-N-methylaminomethyl)phenyl]-N-[2-hydroxyethyl]-4-methoxybenzenesulfonamide). This inhibition was dose-dependent with IC50 values very similar to those that interrupt CaM-dependent reactions in vitro. In contrast, less active analogues of these compounds (1-[6-((17ß-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-2,5-pyrrolidinedione; N-(6-aminohexyl)-1-naphthalenesulfonamide; N-(4-aminobutyl)-1-naphthalenesulfonamide; promethazine; 2-[N-(4- methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzyl-amine]) did not affect activation of Paks in these cells. CaM antagonists (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; trifluoperazine), but not their less-active analogues (N- (6-aminohexyl)-1-naphthalenesulfonamide; promethazine), were also found to block activation of the small GTPases Ras and Rac in stimulated neutrophils along with the extracellular signal-regulated kinases. These data strongly suggest that the Ca^(2+)/CaM complex plays a major role in the activation of a number of enzyme systems in neutrophils that are regulated by small GTPases

Enantiomer Discrimination Illustrated by the High Resolution Crystal Structures of Type 4 Phosphodiesterase †

Type 4 phosphodiesterase (PDE4) inhibitors are emerging new treatment for a number of disorders including asthma and chronic obstructive pulmonary disease. Here we report the biochemical characterization on the second generation inhibitor (+)-1 (L-869298, IC50 = 0.4 nM) and its enantiomer (−)-1 (L-869299, IC50 = 43 nM), and their co-crystal structures with PDE4D at 2.0 Å resolution. In spite of the 107-fold affinity difference, both enantiomers interact with the same sets of residues in the rigid active site. The weaker (−)-1 adopts an unfavorable conformation in order to preserve the pivotal interactions between the Mg-bound waters and N-oxide of pyridine. These structures support a model in which inhibitors are anchored by the invariant glutamine at one end and the metal-pocket residues at another end. This model provides explanation for most of the observed structure-activity relationship and the metal ion dependency of the catechol-ether based inhibitors and should facilitate their further design

Bayesian approach to determining penetrance of pathogenic SDH variants.

BACKGROUND: Until recently, determining penetrance required large observational cohort studies. Data from the Exome Aggregate Consortium (ExAC) allows a Bayesian approach to calculate penetrance, in that population frequencies of pathogenic germline variants should be inversely proportional to their penetrance for disease. We tested this hypothesis using data from two cohorts for succinate dehydrogenase subunits A, B and C (SDHA-C) genetic variants associated with hereditary pheochromocytoma/paraganglioma (PC/PGL). METHODS: Two cohorts were 575 unrelated Australian subjects and 1240 unrelated UK subjects, respectively, with PC/PGL in whom genetic testing had been performed. Penetrance of pathogenic SDHA-C variants was calculated by comparing allelic frequencies in cases versus controls from ExAC (removing those variants contributed by The Cancer Genome Atlas). RESULTS: Pathogenic SDHA-C variants were identified in 106 subjects (18.4%) in cohort 1 and 317 subjects (25.6%) in cohort 2. Of 94 different pathogenic variants from both cohorts (seven in SDHA, 75 in SDHB and 12 in SDHC), 13 are reported in ExAC (two in SDHA, nine in SDHB and two in SDHC) accounting for 21% of subjects with SDHA-C variants. Combining data from both cohorts, estimated lifetime disease penetrance was 22.0% (95% CI 15.2% to 30.9%) for SDHB variants, 8.3% (95% CI 3.5% to 18.5%) for SDHC variants and 1.7% (95% CI 0.8% to 3.8%) for SDHA variants. CONCLUSION: Pathogenic variants in SDHB are more penetrant than those in SDHC and SDHA. Our findings have important implications for counselling and surveillance of subjects carrying these pathogenic variants

Experimental Test of Connector Rotation during DNA Packaging into Bacteriophage ϕ29 Capsids

The bacteriophage ϕ29 generates large forces to compact its double-stranded DNA genome into a protein capsid by means of a portal motor complex. Several mechanical models for the generation of these high forces by the motor complex predict coupling of DNA translocation to rotation of the head-tail connector dodecamer. Putative connector rotation is investigated here by combining the methods of single-molecule force spectroscopy with polarization-sensitive single-molecule fluorescence. In our experiment, we observe motor function in several packaging complexes in parallel using video microscopy of bead position in a magnetic trap. At the same time, we follow the orientation of single fluorophores attached to the portal motor connector. From our data, we can exclude connector rotation with greater than 99% probability and therefore answer a long-standing mechanistic question

Honour and debt release in the parable of the Unmerciful Servant (Mt 18:23–33): A social-scientific and realistic reading

This article presents a social-scientific and realistic reading of the parable of the Unmerciful Servant. The parables of Jesus are realistic stories about everyday events in 1st-century Palestine that evoke specific social realia and practices known to its first hearers. As recent studies on the parables have shown, papyri from early Roman Egypt provide detailed information on the implied social realities and practices assumed in the parables. In reading the parable through the lens of patronage and clientism and against the background of the relationship between royal ideology and debt release attested in documented papyri, it is argued that the parable suggests that in the basileia of God debt should be released in terms of general reciprocity, emulating the way in which patrons release debt for the sake of honour