Predictors of benzodiazepine self -administration behavior in anxious patients

The purpose of this study was to examine factors that may be associated with benzodiazepine (BZ) self-administration and risks of dependence in anxious patients. Preliminary work included examination of psychosocial characteristics and subjective drug response as potential predictors of medication use. Fifty-five M, F patients with generalized anxiety or panic disorder participated in a 3-week outpatient Choice Procedure in which they self-medicated “as needed” with alprazolam (Alz) and placebo. Findings showed that a large amount of variance in alprazolam preference, frequency, and quantity of use could be predicted by measures of anxiety, drug liking, and certain personality characteristics. The primary study extended this work by examining whether individual differences in Alz sensitivity also predict patterns of use. Twenty anxious patients participated in the study, which required 11 weekly clinic visits. Ten of these also participated in a baseline assessment of HPA-axis function that involved 24-hour monitoring of cortisol and ACTH levels and a CRH Stimulation Test. This assessment was conducted on the basis of prior evidence that steroid metabolites exert neuromodulatory effects on the GABA A receptor and that HPA-axis function may be related to BZ sensitivity and long-term disability in anxious patients. Patients were classified as either HIGH or LOW users based on their p.r.n. patterns of Alz use during the first 3 weeks of the study. They then participated in a 4-week dose response trial in which they received prescribed doses of medication (placebo, 0.25, 0.5, and 1.0mg Alz), each taken TID for 1 week. The dose response trial was followed by a second 3-week Choice Procedure. Findings were not indicative of biological differences in Alz sensitivity between the HIGH and LOW users. However, the HIGH users had higher baseline anxiety and greater anxiolytic response to Alz than the LOW users. Anxiolytic benefits of p.r.n. and prescribed dosing were shown to be comparable, and patients' conservative patterns of p.r.n. medication use were not affected by the period of prescribed dosing. Although there was not strong evidence to suggest relationships between HPA-axis function and Alz use or sensitivity, interesting findings emerged about the relationship between HPA-axis function and anxiety. ^

Structural and functional analysis of p84N5

Normal development and tissue homeostasis requires the carefully orchestrated balance between cell proliferation and cell death. Cell cycle checkpoints control the extent of cell proliferation. Cell death is coordinated through the activation of a cell suicide pathway that results in the morphologically recognizable form of death, apoptosis. Tumorigenesis requires that the balance between these two pathways be disrupted. The tumor suppressor protein Rb has not only been shown to be involved in the enforcement of cell cycle checkpoints, but has also been implicated in playing a role in the regulation of apoptosis. The manner in which Rb enforces cell cycle checkpoints has been well studied; however, its involvement in the regulation of apoptosis is still very unclear. p84N5 is a novel nuclear death domain containing protein that has been shown to interact with the N-terminus of Rb. The fact that it contains a death domain and the fact that it is nuclear localized possibly provides the first known mechanism for apoptotic signaling from the nucleus. The following study tested the hypothesis that the novel exclusively nuclear death domain containing protein p84N5 is an important mediator of programmed cell death and that its apoptotic function is reliant upon its nuclear localization and is regulated by unique functional domains within the p84N5 protein. We identified the p84N5 nuclear localization signal (NLS), eliminated it, and tested the functional significance of nuclear localization by using wild type and mutant sequences fused to EGFP-C1 (Clontech) to create wild type GFPN5 and subsequent mutants. The results of these assays demonstrated exclusive nuclear localization of GFPN5 is required for normal p84N5 induced apoptosis. We further conducted large-scale mutagenesis of the GFPN5 construct to identify a minimal region within p84N5 capable of interacting with Rb. We were able to identify a minimal sequence containing p84N5 amino acids 318 to 464 that was capable of interacting with Rb in co-immunoprecipitation assays. We continued by conducting a structural and functional analysis to identify the region or regions within p84N5 responsible for inducing apoptosis. Point mutations and small-scale deletions within the death domain of p84N5 lessened the effect but did not eliminate p84N5-induced cytotoxicity. Further analysis revealed that the minimal sequence of 318 to 464 of p84N5 was capable of inducing apoptosis to a similar degree as wild-type GFPN5 protein. Since amino acids 318 to 464 of p84N5 are capable of inducing apoptosis and interacting with Rb, we propose possible mechanisms whereby p84N5 may function in a Rb regulated manner. These results demonstrate that p84N5 induced apoptosis is reliant upon its nuclear localization and is regulated by unique functional domains within the p84N5 protein. ^

Description and chemical composition of manganese deposits during the deep-sea expedition of the streamer Valdivia in 1898-1899

This monograph forms the fourth part of the tenth volume of the scientific results of the voyage of the German exploring ship Valdivia in the Atlantic and Indian Oceans, made during the years 1898-1899. These volumes are published under the editorship of Prof. Chun, the zoologist of Leipzig, who was leader of the expedition ; and Prof. E. Philippi with the cooperation of Sir John Murray. The nature of the materials brought up at various points during the voyage is well illustrated by a series of plates, similar to those accompanying the Challenger volumes. Among the concretions from the Agulhas Bank were found phosphatic nodules containing 33 per cent, of calcium carbonate, 28 of calcium phosphate, 14.6 of calcium sulphate, and 4.8 of magnesium carbonate, with some ferric oxide, alumina, and silica. These nodules were dredged at a depth of 155 metres. Off the coast of Namibia, a large quantity of manganese nodules were also dredged. Their chemical analysis performed at the Mineralogical Institute of the University Jena show similar composition as the nodules recovered by the "Challenger" at station 253 in the Pacific Ocean.

Annotated record and chemical composition of iron-manganese nodules from the Baltic Sea

Iron-manganese concretions, closely related to lacustrine ores and deep sea manganese nodules, are presently forming in different parts of Gulfs of Bothnia and Finland. They can be divided according to physical form into three distinct groups: (1) round pea-shaped concretions, (2) ring-shaped concrections, and (3) flat sheets and crusts of concretionary material. A definite correlation was found to exist between the form i.e. type of concretions and their chemical composition (Mn/Fe ratio). Trace element concentrations were generally rather high, although not as high as in deep sea manganese nodules. X-ray and DTA was used to study the mineralogy and crystal structure of the concretions. Surface concentrations and geographical distribution of the concretions were estimated on the basis of samples, diving observations and echo-grams.

Description and chemical composition of ferromanganese encrustations and deposits in the Atlantic Ocean from R/V Atlantis II cruises 20, 42, 60, 85; R/V Chain cruise 35; R/V Knorr cruise 61 and RRS Shackleton cruise 75/1 stations

Chemical and mineralogical compositions of ferromanganese oxide coatings on rocks dredged from the New England Seamounts, the Sierra Leone Rise and the Mid-Atlantic Ridge near the Equator have been determined in an investigation of regional differences in Atlantic ferromanganese deposits. Most encrustations are clearly of hydrogenous origin, consisting mainly of todorokite and delta MnO2, but several recovered from the equatorial fracture zones may be hydrothermal accumulations. Differences in the chemistry of the water column and in growth rates of the ferromanganese coatings may be important in producing this regional contrast in composition. Fine-scale changes in element abundances within the encrustations indicate that the nature of the substrate has little influence on compositional variations.

Geochemistry of manganese nodules from a British Columbia fjord

Concretions of iron and manganese oxides and hydrous oxidesóobjects commonly called manganese nodulesóare widely distributed not only on the deep-sea floor but also in shallow marine environments1. Such concretions were not known to occur north of Cape Mendocino in the shallow water zones bordering the North-East Pacific Ocean until the summer of 1966 when they were recovered by one of us (J. W. M.) in dredge samples from Jervis Inlet, a fjord approximately 50 miles north-west of Vancouver, British Columbia.

Description and chemical composition of the fossil manganese nodules of the Cambrian manganese deposits of Conception and Trinity bays, Newfoundland

This paper is based upon data collected during the summers of 1912 and 1913. Mr. A. O. Hayes and Prof. van Ingen of Princeton University, while making a study of the general geology, stratigraphy, and palaeontology of the shores of Conception Bay, Newfoundland, came upon the manganiferous rocks of the Lower Cambrian exposed at Manuels, Topsail, Brigus, and other places. The following summer, of 1913, the writer as a member of the Princeton Newfoundland Expedition undertook a more detailed study of these deposits. In this paper therefore there has been an attempt to present as comprehensive a study of the manganese of southeastern Newfoundland. It is primarily chemical in its nature and the analyses herewith presented are from samples taken from the principal manganese-bearing beds.

Description and chemical composition of ferromanganese deposits from Trout Lake, northern Wisconsin

Sediments were collected with Eckman and Petersen dredges from the bottom of Trout Lake, northern Wisconsin, at 221 stations. Sampling was done with a spud sampler at 32 stations, and core samples were obtained with a Jenkins and Mortimer and a Twenhofel sampler at 17 stations. The shore and offshore deposits of the shores of Trout Lake and the shores of the islands are described. Megascopic descriptions are given of the samples collected with the Eckman and Petersen dredges. Sediments on bottoms of about 10 meters or deeper are mainly gyttja, or crusts composed of mixtures of organic matter, ferric hydroxide, and some form of manganese oxide. The latter deposits are extensive. Detailed descriptions of some of the samples of sands are given, and generalizations respecting size and distribution are made. Tables showing quartiles, medians, and coefficients of sorting and skewness of the coarse sediments collected from the bottom are given in tables. Mechanical analyses of all fine sediments, mainly gyttja, were not made, as previous experience seems to have demonstrated that results have no sedimentational value. Organic matter of the gyttja was determined and also the percentages of lignin in the organic matter. Core samples are composed almost entirely of fine materials, mainly gyttja, and determinations were made on these samples in the same way as on the samples obtained with the Eckman and Petersen dredges. Studies of the core samples show that the fine sediments usually contain in excess of 90 per cent moisture and there is very little change in the moisture content from top to bottom of cores. A map shows the distribution of the iron and manganese deposits. These deposits were found to contain 10 to 20 per cent of organic matter, 11 to 16 per cent of metallic iron, and 12 to 30 per cent of metallic manganese. No stratification of any kind was found in any of the deep-water sediments of Trout Lake except in the iron and manganese crusts. Absence of stratification is considered to be due to the slow rate of deposition and the mixing of sediments by organisms which dwell in them. The data indicate that the rate of deposition in the deep waters of Trout Lake is of the order of 1 foot in 15,000 years.

Annotated record and chemical composition of manganese nodules from station VITYAZ 4575, Indian Ocean

Analyses are given for the core and outer colliform shell of a manganese nodule collected at a depth of 5000 m in the Indian Ocean, and for the red clay that encloses the nodules. Trace elements determined include rare earths, Nb, Ta, Th, and V. The cores of the nodules were once composed of basaltic rock, but now are phillipsite and nontronite. The outer shell is composed of manganite, with admixed quartz, phillipsite, and some geothite. The correlations established between the redox potentials and the concentration coefficients for 12 elements indicate that Eh plays a greater role in the formation of the manganiferous shells than coprecipitation properties.

Description and chemical composition of manganese nodules collected in the Pacific Ocean

Chemical and X-ray analyses were performed on the fifteen manganese nodules collected from the Pacific Ocean floor. The results were discussed compared with the previous data on the manganese nodules. Minerals were found to be todorokite, delta-MnO2 and other silicates, montmorillonite, illite, phillipsite and alpha-Si02. Average composition shows that copper is concentrated on the deep sea nodules more than the shallow ones, and that the todorokite rich nodules contain more copper and nickel than the delta-MnO2 rich ones. The analyses of fresh water iron-manganese precipitates by bacterial activity suggest that biological process is one of the important factors on the genesis of the sedimentary iron-manganese deposits, in¬cluding the manganese nodule.

The amount of water loss was determined by drying at 110°C

Deep-sea deposits, which resemble in nearly every respect the deep-sea oozes have been observed in many islands of the East-Indian Archipelago, notably the islands of Borneo, Rotti and Timor. Manganese nodules are found in equivalents of deeep-sea red clays on Timor and Rotti island. In this paper, those relative to red clay deposits dating from a Cretaceous ocean are analysed in detail in the vicinity of the town of Niki Niki in Western Timor.

Investigation of manganese nodules from the Southern Tasman Sea

Two manganese nodules having a high clay content, a low Mn/Fe ratio, and low contents of valuable metals (Ni 0.25%, Cu 0.17%, Co 0.06%) were recovered in a grab sample during a short geological cruise in HMAS Kimbla in the southern Tasman Sea in May 1979. Five stations were occupied. Free-fall grabs recovered sediment or pumice from four stations; nothing was recovered from the fifth. The carbonate compensation depth in the region is about 4500 m. Reddish brown clay, but no manganese nodules, was recovered in the central southern Tasman Sea, from depths of 4900-5100 m. The nodules, together with grey calcareous mud, were obtained from a depth of 4300 m, farther to the northwest, near Gascoyne Seamount (250 n. miles SE of Sydney). The results suggest nodules with high metal values are likely to exist only in the broad and deep depression in the central southern Tasman Sea southeast of Gascoyne Seamount, where sedimentation rates are low and oxidising conditions prevail. Whether nodule fields are present or not will only be resolved by considerably more sampling.

Studies of the microbial diversity on analyzed samples from from Peru Margin, Equatorial Pacific, Hydrate Ridge, and Juan de Fuca Ridge

Marine sediments harbor an enormous quantity of microorganisms, including a multitude of novel species. The habitable zone of the marine sediment column begins at the sediment-water interface and probably extends to depths of several thousands of meters. Studies of the microbial diversity in this ecosystem have mostly relied on molecular biological techniques. We used a complementary method - analysis of intact polar membrane lipids - to characterize the in-situ microbial community in sediments covering a wide range of environmental conditions from Peru Margin, Equatorial Pacific, Hydrate Ridge, and Juan de Fuca Ridge. Bacterial and eukaryotic phospholipids were only detected in surface sediments from the Peru Margin. In contrast, deeply buried sediments, independent of their geographic location, were dominated by archaeal diether and tetraether lipids with various polar head groups and core lipids. We compared ring distributions of archaeal tetraether lipids derived from polar glycosidic precursors with those that are present as core lipids. The distributions of these related compound pools were distinct, suggestive of different archaeal sources, i.e., the polar compounds derive from sedimentary communities and the core lipids are fossil remnants from planktonic communities with possible admixtures of decayed sedimentary archaea. This in-situ production of distinct archaeal lipid populations potentially affects applications of the TEX86 paleotemperature proxy as demonstrated by offsets in reconstructed temperatures between both pools. We evaluated how varying cell and lipid stabilities will influence the sedimentary pool by using a box-model. The results are consistent with (i) a requirement of continuous inputs of freshly synthesized lipids in subsurface sediments for explaining the observed distribution of intact polar lipids, and (ii) decreasing lipid inputs with increasing burial depth.