Volatile fatty acid production from primary and secondary sludges to support efficient nutrient management.

Enhanced hydrolysis of sludges during fermentation is an important factor to achieve solubilization of complex carbon sources and increase the amount of soluble COD that microorganisms could use as food during biological nutrient removal processes. This research shows that a combination of mixing, bioaugmentation, and co-fermentation can be used to increase the hydrolysis of sludges and enhanced the production of volatile fatty acids (VFA). Mixing of primary sludge (PS) at 350 revolutions per minute (RPM) during fermentation increased the hydrolysis of the sludge and increased the soluble chemical oxygen demand (sCOD) by 72% compared to no mixing.

Sequential hybridization may have facilitated ecological transitions in the Southwestern pinyon pine syngameon.

Multispecies interbreeding networks, or syngameons, have been increasingly reported in natural systems. However, the formation, structure, and maintenance of syngameons have received little attention. Through gene flow, syngameons can increase genetic diversity, facilitate the colonization of new environments, and contribute to hybrid speciation.

Prevalence of non-alcoholic fatty liver disease on computed tomography in patients with inflammatory bowel disease visiting an emergency department.

Background: Non-alcoholic fatty liver disease (NAFLD) is common in patients with inflammatory bowel disease (IBD). The purpose of this study was to further examine the prevalence of NAFLD in IBD patients.

Methods: We retrospectively reviewed the medical records of IBD patients who visited the emergency department because of abdominal pain between January 2009 and December 2014.

American Society of Clinical Oncology 2009 clinical evidence review on radiofrequency ablation of hepatic metastases from colorectal cancer.

Purpose: To review the evidence about the efficacy and utility of radiofrequency ablation (RFA) for hepatic metastases from colorectal cancer (CRHM).

Methods: The American Society of Clinical Oncology (ASCO) convened a panel to conduct and analyze a comprehensive systematic review of the RFA literature from Medline and the Cochrane Collaboration Library.

Results: Because data were considered insufficient to form the basis of a practice guideline, ASCO has instead published a clinical evidence review.

A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint.

Telomeres are complex structures that serve to protect chromosome ends. Here we provide evidence that in Saccharomyces cerevisiae telomeres may contain an anticheckpoint activity that prevents chromosome ends from signaling cell cycle arrest. We found that an internal tract of telomeric repeats inhibited DNA damage checkpoint signaling from adjacent double-strand breaks (DSBs); cell cycle arrest lasted 8-12 h from a normal DSB, whereas it lasted only 1-2 h from a DSB adjacent to a telomeric repeat.

Toward maintaining the genome: DNA damage and replication checkpoints.

DNA checkpoints play a significant role in cancer pathology, perhaps most notably in maintaining genome stability. This review summarizes the genetic and molecular mechanisms of checkpoint activation in response to DNA damage. The major checkpoint proteins common to all eukaryotes are identified and discussed, together with how the checkpoint proteins interact to induce arrest within each cell cycle phase.

Closing the gaps among a web of DNA repair disorders.

As recently as six years ago, three human diseases with similar phenotypes were mistakenly believed to be caused by a single genetic defect. The three diseases, Ataxia-telangiectasia, Nijmegen breakage syndrome, and an AT-like disorder are now known, however, to have defects in three separate genes: ATM, NBS1, and MRE11. Furthermore, new recent studies have shown now that all three gene products interact; the ATM kinase phosphorylates NBS1, which, in turn, associates with MRE11 to regulate DNA repair.

Nuclear DEAF-1-related (NUDR) protein contains a novel DNA binding domain and represses transcription of the heterogeneous nuclear ribonucleoprotein A2/B1 promoter.

Nuclear DEAF-1-related (NUDR) protein is a novel transcriptional regulator with sequence similarity to developmental and oncogenic proteins. NUDR protein deletions were used to localize the DNA binding domain between amino acids 167 and 368, and site-specific DNA photocross-linking indicated at least two sites of protein-DNA contact within this domain. The DNA binding domain contains a proline-rich region and a region with similarity to a Myc-type helix-loop-helix domain but does not include the zinc finger motif at the C terminus.

Characterization of a nuclear deformed epidermal autoregulatory factor-1 (DEAF-1)-related (NUDR) transcriptional regulator protein.

A monkey kidney cDNA that encodes a nuclear regulatory factor was identified by expression and affinity binding to a synthetic retinoic acid response element (RARE) and was used to isolate human placental and rat germ cell cDNAs by hybridization. The cDNAs encode a 59-kDa protein [nuclear DEAF-1-related (NUDR)] which shows sequence similarity to the Drosophila Deformed epidermal autoregulatory factor-1 (DEAF-1), a nonhomeodomain cofactor of embryonic Deformed gene expression. Similarities to other proteins indicate five functional domains in NUDR including an alanine-rich region prevalent in developmental transcription factors, a domain found in the promyelocytic leukemia-associated SP100 proteins, and a zinc finger homology domain associated with the AML1/MTG8 oncoprotein.

Alcohol and other drugs of abuse in pregnancy.

This paper presents an overview of the Mother-Baby Chemical Health Program (MBCHP), which was designed to decrease preterm births among pregnant women who use and abuse drugs. Three hundred and fifty-two patients enrolled in the program between January 1990 and December 1992 were followed. More than 90% of the women involved in the MBCHP did not use substances during their pregnancies.

p-[18F]fluorobenzyltrozamicol ([18F]FBT): molecular decomposition- reconstitution approach to vesamicol receptor radioligands for positron emission tomography.

Current methods of radioligand synthesis for the vesamicol receptor either utilize bioactive unlabeled precursors and/or generate unlabelled bioactive by-products. The presence of these compounds in the radiotracer preparation increases the risk of adverse pharmacological reactions in animals. To eliminate the risk of such reactions, we have synthesized the novel radioligand [18F]FBT from two inactive precursors, [18F]fluorobenzyl iodide and trozamicol.

Synthesis and tissue distribution of (m-[125I]iodobenzyl)trozamicol ([125I]MIBT): potential radioligand for mapping central cholinergic innervation.

Racemic (m-iodobenzyl)trozamicol (6, MIBT), a high-affinity vesamicol receptor ligand, was radiolabeled, resolved, and evaluated in rats. Following iv injection, (+)- and (-)-[125I]MIBT achieved initial brain levels of 0.57 and 0.

Synthesis and biological evaluation of radioiodinated N-2-(4-piperidyl)ethyl benzamides.

Three iodinated benzamides, 5-7, analogues of the potent acetylcholinesterase inhibitor 1-benzyl-4-[N-[4'-(benzylsulfonyl) benzoyl-N-methylamino]ethyl]piperidine (2), were synthesized and evaluated as potential anticholinesterase agents. All three compounds were found to be three orders of magnitude less potent than the parent compound. However, receptor screening revealed that compounds 5-7 exhibit nanomolar affinity for the sigma binding site.

Molecular size and flexibility as determinants of selectivity in the oxidation of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs by monoamine oxidase A and B.

The introduction of a methylene bridge between the phenyl and tetrahydropyridyl moieties of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) results in increased selectivity for monoamine oxidase B (MAO B) over monoamine oxidase A (MAO A). However, lengthening of this bridge results in a total loss of selectivity. In the present study, a number of isomeric 4-naphthyl-, 4-(naphthylalkyl)-, 4-thienyl-, and 4-(thienylalkyl)tetrahydropyridines, conformationally restrained and flexible analogs of MPTP, were synthesized and evaluated as potential selective substrates of MAO A and B.

Lipophilic amino alcohols with calcium channel blocking activity.

A series of novel lipophilic amino alcohols, analogs of the anticholinergic drug vesamicol, were evaluated for Ca2+ channel blocking activity. The effects of these drugs on depolarization-induced intracellular free Ca2+ concentration ([Ca2+]i) transients were examined in single NG108-15 cells and dorsal root ganglion (DRG) neurons in culture. [Ca2+] was recorded with the Ca2+ indicator Indo-1 and a dual emission microfluorimeter.

Interaction of flexible analogs of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and of N-methyl-4-phenylpyridinium with highly purified monoamine oxidase A and B.

Sixteen analogs of N-methyl-1,2,3,6-tetrahydropyridine (MPTP) of varying degrees of flexibility have been studied as substrates of highly purified monoamine oxidases (MAO) A and B. The relative effectiveness of the various tetrahydropyridines as substrates of MAO A and B were evaluated in terms of the function turnover number/Km, as determined by initial rate measurements. The insertion of a methylene bridge between the phenyl and tetrahydropyridine moieties of MPTP to yield N-methyl-4-benzyl-1,2,3,6-tetrahydropyridine, rendering the molecule more flexible, greatly enhances reactivity with MAO B, but not with MAO A, as compared with MPTP itself, in accord with data in the literature (Youngster et al.

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane: potential radiotracer for mapping central cholinergic innervation in vitro.

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane, 5 (4-HIPP), was synthesized and evaluated as a simple vesamicol-like radiotracer for mapping cholinergic pathways in the brain. Both enantiomers of 5 exhibit significant accumulation (approx. 2% of injected dose) and prolonged retention (t1/2 greater than 3 h) within the rat brain.

Magnetic field changes associated with caloric stimulation of the human vestibular organ.

Caloric stimulation of the ear produces a shift of the vestibular resting potential. The current produced by the change in this potential produces a corresponding change in the associated magnetic field. A sensitive magnetic detector (second-derivative gradiometer) was used to detect a large shift in the magnetic field close to the ears of two normal subjects who underwent cold thermic ear stimulation.

Acyclic analogues of 2-(4-phenylpiperidino)cyclohexanol (vesamicol): conformationally mobile inhibitors of vesicular acetylcholine transport.

Several 1,3-disubstituted propan-2-ols and one alpha,beta-disubstituted ethanol (11i) were synthesized and evaluated as potential acyclic mimics of the vesicular acetylcholine transport inhibitor 2-(4-phenylpiperidinyl)cyclohexanol (1, vesamicol, AH5183). Analogues containing the 4-phenylpiperidyl fragment (11a, 11b) were more potent than those containing the 4-phenylpiperazyl moiety (11e, 11f). Substitution at the second terminal carbon of the propyl (or ethyl) fragment with simple lipophilic aryl substituents yielded potent inhibitors of vesicular acetylcholine storage, including (-)-11a and d-11i, which are equipotent with vesamicol.

Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: synthesis and monoamine oxidase catalyzed bioactivation.

Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.

A new alkaline phosphatase isoenzyme abnormality.

We report on a new alkaline phosphatase isoenzyme abnormality occurring as an incidental finding in a male infant aged 4 months. Isoenzyme electrophoresis on cellulose acetate showed a prominent, diffuse alkaline phosphatase staining band in the alpha 1-globulin position together with a second band in the alpha 2/beta region and minor 'trailing' in the intermediate alpha 2 region. Normal liver and bone alkaline phosphatase were absent and intestinal phosphatase was not detected.