Epigenetic upregulation of Bak by ZBP-89 inhibits the growth of hepatocellular carcinoma

Zinc-binding protein-89 regulates Bak to facilitate apoptosis in cancer cells. This study examined if zinc-binding protein-89 regulates Bak through an epigenetic mechanism in hepatocellular carcinoma. We first demonstrated that the expression of Bak was reduced but the levels of deoxyribonucleic acid methyltransferase 1 and histone deacetylase 3 were increased in hepatocellular carcinoma cancer tissues compared to the corresponding non-cancer tissues. Moreover, there was a negative correlation between Bak expression and deoxyribonucleic acid methyltransferase 1 levels in hepatocellular carcinoma. Administration of zinc-binding protein-89 downregulated histone deacetylase 3 expression and suppressed the activities of histone deacetylase and deoxyribonucleic acid methyltransferase, which led to maintenance of histone acetylation status, inhibited the binding of methyl-CpG-binding protein 2 to genomic deoxyribonucleic acid and demethylated CpG islands in the Bak promoter in hepatocellular carcinoma cells. Using the xenograft mouse tumor model, we demonstrated that zinc-binding protein-89 or inhibitors of either epigenetic enzymes could stimulate Bak expression, induce apoptosis, and arrest tumor growth and that the maximal effort was achieved when zinc-binding protein-89 and the enzyme inhibitors were used in combination. Conclusively, zinc-binding protein-89 upregulates the expression of Bak by targeting multiple components of the epigenetic pathway in hepatocellular carcinoma.     

Renal ultrasonography and detection of pseudomycelium in urine as means of diagnosis of renal fungus balls in neonates

Objective. To present a series of neonates with renal fungus balls diagnosed by ultrasonography, urine culture and/or by the detection of Candida pseudomycelium in urine. Patients and methods. We revised the clinical records of neonates for whom the diagnosis of renal fungus ball was established by ultrasound and laboratory studies; these patients had been hospitalized at the National Institute of Pediatrics in Mexico between January 1st, 1999 and December 31st, 2002. Results. During the study period, 9 neonates were diagnosed with renal fungus ball. In 7 cases, the ethiologic agent was Candida albicans; whereas it was C. tropicalis in one case and C. parapsilosisin the other. Urine culture was positive (10,000 UFC/ml) in 8 cases, whereas the fungal density was only 2400UFC/ml in the last sample. Pseudohyphae were present in all cases and ultrasonography showed fungus ball in every case. All patients received a single antifungal drug, either amphotericin B or fluconazole. All the patients recovered and none of them required surgical treatment. Control postreatment by ultrasound studies showed that the fungus balls had disappeared in every case. Conclusion. The diagnosis of Candida renal fungus balls based on the ultrasound study and urine culture is also substantiated by the detection of pseudomycelium in the centrifugation pellet of urine samples, which is a fast diagnostic method. This approach permitted an early diagnosis and treatment of Candida renal fungus balls.     

Evidence of chemical reactions between di- and poly-glycidyl ether resins and tannins isolated from Pinus radiata D. Don bark

This work evaluates the feasibility of reacting tannins isolated from Pinus radiata D. Don bark with epoxide resins of the diglycidyl and polyglycidyl ether type. To this end, gel times of aqueous tannin dispersions (40% w/w) with every one of nine selected resins (5% w/w), at previously established pH values (initial equal to 3.3, 4, 7 and 10), have been determined. Products of these reactions were analyzed by FT-IR spectroscopy, and the results were compared with those obtained from tannin-p-formaldehyde and (+)-catechin-p-formaldehyde systems, at the same pH values. Their mechanical properties were evaluated, by dynamic mechanical analysis, at two pH values (3.3 and 10). In general, it was concluded that tannin-epoxide resin systems behave similarly to tannin-paraformaldehyde systems, especially at basic pH values.     

The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs

A better understanding of the mechanisms through which anticancer drugs exert their effects is essential to improve combination therapies. While studying how genotoxic stress kills cancer cells, we discovered a large ～2MDa cell death-inducing platform, referred to as "Ripoptosome." It contains the core components RIP1, FADD, and caspase-8, and assembles in response to genotoxic stress-induced depletion of XIAP, cIAP1 and cIAP2. Importantly, it forms independently of TNF, CD95L/FASL, TRAIL, death-receptors, and mitochondrial pathways. It also forms upon Smac-mimetic (SM) treatment without involvement of autocrine TNF. Ripoptosome assembly requires RIP1's kinase activity and can stimulate caspase-8-mediated apoptosis as well as caspase-independent necrosis. It is negatively regulated by FLIP, cIAP1, cIAP2, and XIAP. Mechanistically, IAPs target components of this complex for ubiquitylation and inactivation. Moreover, we find that etoposide-stimulated Ripoptosome formation converts proinflammatory cytokines into prodeath signals. Together, our observations shed new light on fundamental mechanisms by which chemotherapeutics may kill cancer cells.     

The enigma of the CLIC proteins: Ion channels, redox proteins, enzymes, scaffolding proteins?

Chloride intracellular channel proteins (CLICs) are distinct from most ion channels in that they have both soluble and integral membrane forms. CLICs are highly conserved in chordates, with six vertebrate paralogues. CLIC-like proteins are found in other metazoans. CLICs form channels in artificial bilayers in a process favoured by oxidising conditions and low pH. They are structurally plastic, with CLIC1 adopting two distinct soluble conformations. Phylogenetic and structural data indicate that CLICs are likely to have enzymatic function. The physiological role of CLICs appears to be maintenance of intracellular membranes, which is associated with tubulogenesis but may involve other substructures.     

Degradation of Tribromophenol by Wood-Decaying Fungi and the 1,2-Dihydroxybenzene-Assisted Fenton Reaction

The degradation of 2,4,6-tribromophenol (TBP) by biological and chemical treatments was studied. Biological treatment involved the use of Laetoporeus sulfureus, Gloephyllum trabeum, and Ganoderma australe in liquid culture. Despite the inhibitory effects of TBP on the fungal growth, these fungi were able to degrade TBP after 15 days of biotreatment. At 66, 116, and 183 μ M TBP, the degradation by G. australe was the most efficient (71% to 77%), whereas G. trabeum and L. sulfureus degraded between 50% and 60% of three TBP concentrations. The removal of organic bromine reached values of 50% in all cases. The chemical treatment (1,2-dihydroxybenzene-assisted Fenton reaction) achieved up to 90% of TBP degradation. However, only 40% of TBP was mineralized and the toxicity level did not undergo changes during the chemical treatment. On the other hand, a 30% reduction in toxicity was obtained with a combined chemical-biological treatment.     

Conditional deletion of menin results in antral G cell hyperplasia and hypergastrinemia

Antral gastrin is the hormone known to stimulate acid secretion and proliferation of the gastric corpus epithelium. Patients with mutations in the multiple endocrine neoplasia type 1 (MEN1) locus, which encodes the protein menin, develop pituitary hyperplasia, insulinomas, and gastrinomas in the duodenum. We previously hypothesized that loss of menin leads to derepression of the gastrin gene and hypergastrinemia. Indeed, we show that menin represses JunD induction of gastrin in vitro. Therefore, we examined whether conditional deletion of Men1 (Villin-Cre and Lgr5-EGFP-IRES-CreERT2), with subsequent loss of menin from the gastrointestinal epithelium, increases gastrin expression. We found that epithelium-specific deletion of Men1 using Villin-Cre increased plasma gastrin, antral G cell numbers, and gastrin expression in the antrum, but not the duodenum. Moreover, the mice were hypochlorhydric by 12 mo of age, and gastric somatostatin mRNA levels were reduced. However, duodenal mRNA levels of the cyclin-dependent kinase inhibitor p27(Kip1) were decreased, and cell proliferation determined by Ki67 staining was increased. About 11% of the menin-deficient mice developed antral tumors that were negative for gastrin; however, gastrinomas were not observed, even at 12 mo of age. No gastrinomas were observed with conditional deletion of Men1 in the Lgr5 stem cells 5 mo after Cre induction. In summary, epithelium-specific deletion of the Men1 locus resulted in hypergastrinemia due to antral G cell hyperplasia and a hyperproliferative epithelium, but no gastrinomas. This result suggests that additional mutations in gene targets other than the Men1 locus are required to produce gastrin-secreting tumors.     

New records of spider wasps (Hymenoptera,Pompilidae) from Colombia

New records of genera and species of spider wasps (Hymenoptera: Pompilidae) from Colombia are provided. Agenioideus, Cryptocheilus, Evagetes, Mystacagenia, and Xerochares are newly recorded genera from Colombia. Nineteen species are first recorded from Colombia: Aimatocare vitrea (Fox); Ageniella azteca (Cameron); Ageniella curtipinus (Cameron); Ageniella fallax (Arlé); Ageniella hirsuta Banks; Ageniella pilifrons (Cameron); Ageniella pretiosa Banks; Ageniella sanguinolenta (Smith); Ageniella zeteki (Banks); Agenioideus birkmanni (Banks); Aporus (Aporus) cuzco Evans; Aporus (Cosmiaporus) diverticulus (Fox); Aporus (Notoplaniceps) canescens Smith; Euplaniceps exilis (Banks); Euplaniceps herbertii (Fox); Irenangelus clarus Evans; Mystacagenia bellula Evans; Phanochilus nobilitatus (Smith) and Xerochares expulsus Schulz. The following species and genera have their occurence ranges expanded for South America: Ageniella azteca (Cameron); Ageniella zeteki (Banks); Agenioideus birkmanni (Banks); and Xerochares expulsus Schulz; Cryptocheilus Panzer; and Xerochares Evans.     

Variation in barley (1 → 3, 1 → 4)-β-glucan endohydrolases reveals novel allozymes with increased thermostability

Key message

Novel barley (1 → 3, 1 → 4)-β-glucan endohydrolases with increased thermostability.

Abstract

Rapid and reliable degradation of (1 → 3, 1 → 4)-β-glucan to produce low viscosity wort is an essential requirement for malting barley. The (1 → 3, 1 → 4)-β-glucan endohyrolases are responsible for the primary hydrolysis of cell wall β-glucan. The variation in β-glucanase genes HvGlb1 and HvGlb2 that encode EI and EII, respectively, were examined in elite and exotic germplasm. Six EI and 14 EII allozymes were identified, and significant variation was found in β-glucanase from Hordeum vulgare ssp. spontaneum (wild barley), the progenitor of modern cultivated barley. Allozymes were examined using prediction methods; the change in Gibbs free energy of the identified amino acid substitutions to predict changes in enzyme stability and homology modelling to examine the structure of the novel allozymes using the existing solved EII structure. Two EI and four EII allozymes in wild barley accessions were predicted to have improved barley β-glucanase thermostability. One novel EII candidate was identified in existing backcross lines with contrasting HvGlb2 alleles from wild barley and cv Flagship. The contrasting alleles in selected near isogenic lines were examined in β-glucanase thermostability analyses. The EII from wild barley exhibited a significant increase in β-glucanase thermostability conferred by the novel HvGlb2 allele. Increased β-glucanase thermostability is heritable and candidates identified in wild barley could improve malting and brewing quality in new varieties.