Nest-moving by the polydomous ant <Emphasis Type="Italic">Cataglyphis iberica</Emphasis>

In this paper we analyze emigration from nests by the polydomous ant Cataglyphis iberica. Social carrying of workers of this species between different nests of the colony is frequent. In Bellaterra (Barcelona, NE Spain), we monitored field emigration of C. iberica by noting for each nest the migratory behavior of C. iberica workers and, when the nests were attacked by another ant species, Camponotus foreli, we noted the number of C. foreli workers involved in the attacks. Emigration of C. iberica from nests was highly variable. We suggest the main factor determining emigration by this species was attack by workers of C. foreli, so emigration from C. iberica nests was much faster when harassment by C. foreli increased. The system of multiple nests of C. iberica enables this species to abandon attacked nests and to reinstall their population in other nests of the same colony. This reduces risk to the colonies because the route between the different nests is well known by transporter workers.     

Suppression of c-Myc-Induced Apoptosis by the Epstein-Barr Virus Gene Product BHRF1

Constitutive expression of the c-myc proto-oncogene in growth factor-deprived fibroblasts promotes proliferation and induces apoptosis. In these cells, apoptosis can be inhibited by survival factors such as insulin-like growth factor I or the bcl-2 proto-oncogene product. Deregulated c-Myc expression is a common feature in Epstein-Barr virus-positive Burkitt’s lymphoma in which the c-myc gene is reciprocally translocated and placed under the control of one of the immunoglobulin loci. BHRF1 is an Epstein-Barr virus protein expressed early in the lytic cycle. BHRF1 is a member of the Bcl-2 family and has been shown to suppress apoptosis and to increase cell survival in different settings. In the present study, we report that BHRF1 inhibits c-Myc-induced apoptosis which occurs in the absence of survival factors. It does not, however, affect the capacity of c-Myc to promote cell growth. These findings demonstrate that BHRF1 has not only structural but also functional similarities to Bcl-2.     

Bio-Acidification and Leaching of Metals,Nitrogen, and Phosphorus from Soil and Sludge Mixtures

Soil and wastewater treatment sludge are commonly brought together in mixtures for a variety of beneficial purposes. The mixtures contain bioacidifying (i.e., sulfur-oxidizing) microorganisms that can easily be activated through providing the appropriate substrate and environmental conditions. In this study, contaminated soil and sludge mixtures were subjected to controlled bio-acidification and the impacts of the process on the partitioning of heavy metals, nitrogen, and phosphorus were examined. Three successive bio-acidification cycles resulted in significant leaching of metals from sludge. The leaching results, expressed as fraction of total mass of metals in the sludge, averaged 67% for Cr, 96% for Ni, 24% for Zn; 16% for Cu; 23% for Cd; and 96% for Pb. Bio-acidification of the sludge also converted 28 to 45% of the organic nitrogen into ammonia and increased the soluble orthophosphates fraction of total phosphorus by approximately 18 to 20%. Bio-acidification also resulted in significant metals leaching from the contaminated soils in the soil/sludge mixtures. Soil/sludge mixtures were prepared using six soil particle sizes (less than 0.075?mm to 2.38?mm) contaminated with 22,500?mg/kg Zn, 14,000?mg/kg Pb, 1500?mg/kg Cr, 9500?mg/kg Cu, 1000?mg/kg Ni, and 1000?mg/kg Cd. The addition of metals to the soil inhibited the sulfur-oxidizing microorganisms, preventing bio-acidification in the mixtures containing 4 to 50?g soil in 130?ml sludge, and considerably slowing bio-acidification in the mixtures containing 1 to 3?g soil. Using a mixture that contained 2-g soil samples, three successive bio-acidification cycles resulted in significant cumulative metals leaching results. The leaching results, expressed as percentage of the mass of metals added to the soil, were in the range of 56 to 98% for Cr, 77 to 95% for Zn, 33 to 66% for Ni, 64 to 82% for Cu, and 10 to 33% for Pb, with the higher results in each range belonging to the larger size soil particles. On the other hand, only Cr was leached in neutralized soil samples. The results confirmed the potential for inhibition of the sulfur-oxidizing microorganisms and bio-acidification in contaminated soil/sludge mixtures, and the significant impacts of bio-acidification on the mobility of metals, nitrogen, and phosphorus. In addition, the results confirmed the potential for using controlled bioacidification for removing heavy metals from contaminated soil using the indigenous sulfur oxidizing microorganisms in sludge.     

Pharmacologic characterization of muscarinic receptors of insect brains.

Muscarinic receptors in brain membranes from honey bees, houseflies, and the American cockroach were identified by their specific binding of the non-selective muscarinic receptor antagonist [3H]quinuclidinyl benzilate ([3H]QNB) and the displacement of this binding by agonists as well as subtype-selective antagonists, using filtration assays. The binding parameters, obtained from Scatchard analysis, indicated that insect muscarinic receptors, like those of mammalian brains, had high affinities for [3H]QNB (KD = 0.47 nM in honey bees, 0.17 nM in houseflies and 0.13 nM in the cockroach). However, the receptor concentration was low (108, 64.7, and 108 fmol/mg protein for the three species, respectively). The association and dissociation rates of [3H]QNB binding to honey bee brain membranes, sensitivity of [3H]QNB binding to muscarinic agonists, and high affinity for atropine were also features generally similar to muscarinic receptors of mammalian brains. In order to further characterize the three insect brain muscarinic receptors, the displacement of [3H]QNB binding by subtype-selective antagonists was studied. The rank order of potency of pirenzepine (PZ), the M1 selective antagonist, 11-[2-[dimethylamino)-methyl)1-piperidinyl)acetyl)-5,11- dihydro-6H-pyrido(2,3-b)-(1,4)-benzodiazepin-6 one (AF-DX 116), the M2-selective antagonist, and 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide) the M3-selective antagonist, was also the same as that of mammalian brains, i.e., 4-DAMP greater than PZ greater than AF-DX 116. The three insect brain receptors had 27-50-fold lower affinity for PZ (Ki 484-900 nM) than did the mammalian brain receptor (Ki 16 nM), but similar to that reported for the muscarinic receptor subtype cloned from Drosophila. Also, the affinity of insect receptors for 4-DAMP (Ki 18.9-56.6 nM) was much lower than that of the M3 receptor, which predominates in rat submaxillary gland (Ki of 0.37 nM on [3H]QNB binding). These drug specificities of muscarinic receptors of brains from three insect species suggest that insect brains may be predominantly of a unique subtype that is close to, though significantly different from, the mammalian M3 subtype.     

Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function

Acute, inflammatory conditions associated with dysregulated complement activation are characterized by significant increases in blood concentration of reactive oxygen species (ROS) and ATP. The mechanisms by which these molecules arise are not fully understood. In this study, using luminometric- and fluorescence-based methods, we show that ligation of glycophorin A (GPA) on human red blood cells (RBCs) results in a 2.1-fold, NADPH-oxidase-dependent increase in intracellular ROS that, in turn, trigger multiple downstream cascades leading to caspase-3 activation, ATP release, and increased band 3 phosphorylation. Functionally, using 2D microchannels to assess membrane deformability, GPS-ligated RBCs travel 33% slower than control RBCs, and lipid mobility was hindered by 10% using fluorescence recovery after photobleaching (FRAP). These outcomes were preventable by pretreating RBCs with cell-permeable ROS scavenger glutathione monoethyl ester (GSH-ME). Our results obtained in vitro using anti-GPA antibodies were validated using complement-altered RBCs isolated from control and septic patients. Our results suggest that during inflammatory conditions, circulating RBCs significantly contribute to capillary flow dysfunctions, and constitute an important but overlooked source of intravascular ROS and ATP, both critical mediators responsible for endothelial cell activation, microcirculation impairment, platelet activation, as well as long-term dysregulated adaptive and innate immune responses.     

Contaminated Heparin and Outcomes after Cardiac Surgery: A Retrospective Propensity-Matched Cohort Study

Background

During 2007 and 2008 it is likely that millions of patients in the US received heparin contaminated (CH) with oversulfated chondroitin sulfate, which was associated with anaphylactoid reactions. We tested the hypothesis that CH was associated with serious morbidity, mortality, intensive care unit (ICU) stay and heparin-induced thrombocytopenia following adult cardiac surgery.

Methods and Findings

We conducted a single center, retrospective, propensity-matched cohort study during the period of CH and the equivalent time frame in the three preceding or the two following years. Perioperative data were obtained from the institutional record of the Society of Thoracic Surgeons National Database, for which the data collection is prospective, standardized and performed by independent investigators. After matching, logistic regression was performed to evaluate the independent effect of CH on the composite adverse outcome (myocardial infarction, stroke, pneumonia, dialysis, cardiac arrest) and on mortality. Cox regression was used to determine the association between CH and ICU length of stay. The 1∶5 matched groups included 220 patients potentially exposed to CH and 918 controls. There were more adverse outcomes in the exposed cohort (20.9% versus 12.0%; difference = 8.9%; 95% CI 3.6% to 15.1%, P<0.001) with an odds ratio for CH of 2.0 (95% CI, 1.4 to 3.0, P<0.001). In the exposed group there was a non-significant increase in mortality (5.9% versus 3.5%, difference = 2.4%; 95% CI, −0.4 to 3.5%, P = 0.1), the median ICU stay was longer by 14.1 hours (interquartile range −26.6 to 79.8, S = 3299, P = 0.0004) with an estimated hazard ratio for CH of 1.2 (95% CI, 1.0 to 1.4, P = 0.04). There was no difference in nadir platelet counts between cohorts.

Conclusions

The results from this single center study suggest the possibility that contaminated heparin might have contributed to serious morbidity following cardiac surgery.     

An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme

In the ubiquitin-proteasome system (UPS), E2 enzymes mediate the conjugation of ubiquitin to substrates and thereby control protein stability and interactions. The E2 enzyme hCdc34 catalyzes the ubiquitination of hundreds of proteins in conjunction with the cullin-RING (CRL) superfamily of E3 enzymes. We identified a small molecule termed CC0651 that selectively inhibits hCdc34. Structure determination revealed that CC0651 inserts into a cryptic binding pocket on hCdc34 distant from the catalytic site, causing subtle but wholesale displacement of E2 secondary structural elements. CC0651 analogs inhibited proliferation of human cancer cell lines and caused accumulation of the SCF(Skp2) substrate p27(Kip1). CC0651 does not affect hCdc34 interactions with E1 or E3 enzymes or the formation of the ubiquitin thioester but instead interferes with the discharge of ubiquitin to acceptor lysine residues. E2 enzymes are thus susceptible to noncatalytic site inhibition and may represent a viable class of drug target in the UPS.     

SH3‐class Ras guanine nucleotide exchange factors are essential for Aspergillus fumigatus invasive growth

Proper hyphal morphogenesis is essential for the establishment and progression of invasive disease caused by filamentous fungi. In the human pathogen Aspergillus fumigatus, signalling cascades driven by Ras and Ras‐like proteins orchestrate a wide variety of cellular processes required for hyphal growth. For activation, these proteins require interactions with Ras‐subfamily‐specific guanine nucleotide exchange factors (RasGEFs). Although Ras‐protein networks are essential for virulence in all pathogenic fungi, the importance of RasGEF proteins is largely unexplored. A. fumigatus encodes four putative RasGEFs that represent three separate classes of RasGEF proteins (SH3‐, Ras guanyl nucleotide‐releasing protein [RasGRP]–, and LTE‐class), each with fungus‐specific attributes. Here, we show that the SH3‐class and RasGRP‐class RasGEFs are required for properly timed polarity establishment during early growth and branch emergence as well as for cell wall stability. Further, we show that SH3‐class RasGEF activity is essential for polarity establishment and maintenance, a phenotype that is, at least, partially independent of the major A. fumigatus Ras proteins, RasA and RasB. Finally, loss of both SH3‐class RasGEFs resulted in avirulence in multiple models of invasive aspergillosis. Together, our findings suggest that RasGEF activity is essential for the integration of multiple signalling networks to drive invasive growth in A. fumigatus.     

Noncytotoxic Dy3+-activated glass emits cool white light for near ultraviolet-based white light-emitting diodes,visible lasers,and biomedical applications

Using the melt quenching technique, a lithium zinc borate glass (LZB) system with trivalent dysprosium ions (Dy³⁺) was synthesized, and the luminescence and lasing properties of these materials were examined for the generation of white light. Structural investigation through X-ray diffraction revealed that the prepared glass had an amorphous nature. The optimized glass containing 0.5 Dy³⁺ had a direct optical band gap of 2.782 eV and an indirect optical band gap of 3.110 eV. A strong excitation band at 386 nm (⁶H_15/2→⁴I_13/2) was recognized in the ultraviolet (UV) light region of its excitation spectrum. Emission bands could be seen in the photoluminescence spectrum at 659, 573, and 480 nm under the 386 nm excitation. These transitions of emission resembled electronic transitions such as (⁴F_9/2→⁶H_11/2), (⁴F_9/2→⁶H_13/2), and (⁴F_9/2→⁶H_15/2). In a pristine glass matrix, the higher intensity ratio of yellow to blue can result in the production of white light. The optimized Dy³⁺ ion concentration was observed to be 0.5 mol%. In addition, an analysis of lifetime decay was conducted for all synthesized glasses, and their decay trends were systematically investigated. Noticeably, we assessed the photometric parameters and found that they were close to the white light standard. Furthermore, a cytotoxicity study was carried out using lung fibroblast (WI-38) cell lines for the optimized 0.5Dy³⁺-doped LZB glass and it appeared to be noncytotoxic. It is clear from the results that the noncytotoxic LZB glass doped with 0.5 Dy³⁺ ions could be a suggestive choice for the manufacture of white light-emitting diodes and lasers using near-UVs.