Alterations of the Characteristics of the Circadian Rest‐Activity Rhythm of Cancer In‐Patients

The aim of the present study was to evaluate the characteristics of the circadian rest‐activity rhythm of cancer patients. Thirty‐one in‐patients, consisting of 19 males and 12 females, were randomly selected from the Regional Cancer Center, Pandit Jawaharlal Nehru Medical College, Raipur, India. The rest‐activity rhythm was studied non‐invasively by wrist actigraphy, and compared with 35 age‐matched apparently healthy subjects (22 males and 13 females). All subjects wore an Actiwatch (AW64, Mini Mitter Co. Inc., USA) for at least 4–7 consecutive days. Fifteen‐second epoch length was selected for gathering actigraphy data. In addition, several sleep parameters, such as time in bed, assumed sleep, actual sleep time, actual wake time, sleep efficiency, sleep latency, sleep bouts, wake bouts, and fragmentation index, were also recorded. Data were analyzed using several statistical techniques, such as cosinor rhythmometry, spectral analysis, ANOVA, Duncan's multiple‐range test, and t‐test. Dichotomy index (I<O) and autocorrelation coefficient (r24) were also computed. The results validated a statistically significant circadian rhythm in rest‐activity with a prominent period of 24 h for most cancer patients and control subjects. Results of this study further revealed that cancer patients do experience a drastic alteration in the circadian rest‐activity rhythm parameters. Both the dichotomy index and r24 declined in the group of cancer patients. The occurrence of the peak (acrophase, Ø) of the rest‐activity rhythm was earlier (p<0.001) in cancer patients than age‐ and gender‐matched control subjects. Results of sleep parameters revealed that cancer patients spent longer time in bed, had longer assumed and actual sleep durations, and a greater number of sleep and wake bouts compared to control subjects. Further, nap frequency, total nap duration, average nap, and total nap duration per 1 h awake span were statistically significantly higher in cancer patients than control subjects. In conclusion, the results of the present study document the disruption of the circadian rhythm in rest‐activity of cancer in‐patients, with a dampening of amplitude, lowering of mean level of activity, and phase advancement. These alterations of the circadian rhythm characteristics could be attributed to disease, irrespective of variability due to gender, sites of cancer, and timings of therapies. These results might help in designing patient‐specific chronotherapeutic protocols.     

Photoanalogues of the Initiation Substrates of the RNA Polymerase II, 5‐Azido‐2‐Nitrobenzoyl Derivatives of the ATP γ‐Amidophosphate: The Possible Photoinduced Degradation of the Functional Group to an N‐Arylhydroxylamine

Photoanlogues of the initiation substrates of the RNA polymerase II, N₃Ar‐ NH(CH₂)_nNHpppA where N₃Ar is 5‐azido‐2‐nitrobenzoyl group (n = 2 or 4) were synthesized, allowing the preparation of photoreactive oligonucleotides in situ by RNA polymerase II for application as photolabels. Photolysis of p‐nitro‐substituted aromatic azide in aqueous medium was investigated. Using the azoxy‐coupling reaction it was possible to determine whether a nitrene or p‐nitrophenyl hydroxylamine azoxy compound is the trappable intermediate that is generated at ambient temperature in aqueous solution.     

Plants‐associated microflora and the remediation of oil‐contaminated soil

The use of plants and their rhizospheric microorganisms is a promising emerging technology for remediating contaminated soils. The degradation of total petroleum hydrocarbon (TPH) in the rhizospheric and nonrhizospheric soil of three domestic plants, namely, alfalfa (Medicaga sativa) broad beans (Vicia faba) and ryegrass (Lolium perenne) was investigated. The experimental data from the studies of plantmicrobe‐soil interactions implicated the enhancement of TPH degradation by the rhizospheric microbial community. Although the three domestic plants exhibited normal growth in the presence of ～1.0% TPH, the degradation was more profound in the case of leguminous plants. The TPH degradation in the soil cultivated with broad beans and alfalfa was 36.6 and 35.8%, respectively, compared with 24% degradation in case of ryegrass. Such a high correlation between plant type and TPH degradation rates indicate that selection for enhanced rhizosphere degradation may be accomplished by selecting leguminous plants.     

Building cross‐cultural coalitions: A case‐study of the Black‐Korean Alliance and the Latino‐Black Roundtable

A case‐study is presented of two Los Angeles‐based cross‐cultural coalitions, the Black‐Korean Alliance [BKA] and the Latino‐Black Roundtable [LBR]. An analysis of the development and eventual dissolution of these two coalitions is presented against the backdrop of the history of relations between the African‐American, Korean‐American and Latino communities of Los Angeles. The central issues leading to the breakup of the two coalitions were: lack of resources, internal power dynamics between coalition partners, nationalistic factions within the broader communities, cross‐cultural dynamics between coalition members, the use of a dialogue model to frame coalition activities, and the analysis of intergroup relations underlying the formation of the coalitions. The applied and theoretical implications of the research are discussed.     

Synthesis of Oligoribonucleotides Containing 4‐Thiouridine Using the Convertible Nucleoside Approach and the 1‐(2‐Fluorophenyl)‐4‐Methoxypiperidin‐4‐yl Group

Oligoribonucleotides containing 4‐thiouridine were prepared using the Fpmp group for protection of the 2′‐OH. Two uridine derivatives with the 1,2,4‐triazolyl and the 2‐nitrophenyl groups at position 4 were used to obtain 4‐thiouridine by postsynthetic substitution with sodium hydrogen sulfide. Both uridine derivatives allow the preparation of the desired oligonucleotides in good yields.     

Micro‐mechanical measurement of the torsional modulus of DNA

The torsional modulus C of DNA is determined from the difference between the work of stretching a single overwound molecule and the work done in stretching one underwound by the same number of turns. The value obtained C/k_BT=86±10 nm is within the range (75±25 nm) estimated by more indirect methods.This revised version was published online in October 2005 with corrections to the Cover Date.     

Circadian Variations in the Activities of 6‐Phosphogluconate Dehydrogenase and Glucose‐6‐Phosphate Dehydrogenase in the Liver of Conrol and Streptozotocin‐Induced Diabetic Rats

The aim of this study was to examine: the 24 h variation of 6‐phosphogluconate dehydrogenase and glucose‐6‐phosphate dehydrogenase activities, key enzymes for the maintenance of intracellular NADPH concentration, in rat liver in control and streptozotocin‐induced diabetic animals. Adult male rats were fed ad libitum and synchronized on a 12:12 h light‐dark cycle (lights on 08:00 h). One group of animals was treated with streptozotocin (STZ, 55 mg/kg, intraperitoneal) to induce experimental diabetes. Eight weeks after STZ injection, the animals were sacrificed at six different times of day—1, 5, 9, 13, 17 and 21 Hours After Lights On (HALO)—and livers were obtained. Enzyme activities were determined spectrophotometrically in triplicate in liver homogenates and expressed as units per mg protein. 6‐phosphogluconate dehydrogenase activity was measured by substituting 6‐phosphogluconate as substrate. Glucose‐6‐phosphate dehydrogenase activity was determined by monitoring NADPH production. Treatment, circadian time, and interaction between treatment and circadian time factors were tested by either one or two way analysis of variance (ANOVA). Two‐way ANOVA revealed that 6‐phosphogluconate dehydrogenase activity significantly depended on both the treatment and time of sacrifice. 6‐phosphogluconate dehydrogenase activity was higher in control than diabetic animals; whereas, glucose‐6‐phosphate dehydrogenase activity did not vary over the 24 h in animals made diabetic by STZ treatment. Circadian variation in the activity of 6‐phosphogluconate dehydrogenase was also detected in both the control and STZ treatment groups (one‐way ANOVA). Time‐dependent variation in glucose‐6‐phosphate dehydrogenase activity during the 24 h was detected in control but not in diabetic rats. No significant interaction was detected between STZ‐treatment and time of sacrifice for both hepatic enzyme activities. These results suggest that the activities of NADPH‐generating enzymes exhibit 24 h variation, which is not influenced by diabetes.     

Seasonal Modulation of the 8‐and 24‐Hour Rhythms of Ondansetron Tolerance in Mice

Ondansetron (Zophren®) is a serotonin 5HT₃-receptor antagonist used primarily to control nausea and vomiting caused by cytotoxic chemo‐and radio‐therapy. Tolerance to this drug shows both 24 and 8 h periodicities. In this framework, this study aimed to determine whether these ondansetron tolerance rhythms are modulated by season. The chronotoxic effect of a fixed dose (3.5 mg/kg, i.p.) of the drug was investigated with reference to both time of the day and year dependencies. Season‐related studies were performed on 560 male Swiss mice, 10 to 12 wks old, synchronized with L:D=12:12 for three weeks. During a 1 yr span (2005), four 24 h studies were performed with a single dosing time at 1, 7, 13, and 19 hours after light onset (HALO), respectively. Tolerance was assessed daily during a 40‐day span after acute ondansetron treatment. Both χ² test and cosinor methods were used to analyze the time series data. Statistically significant dosing time‐dependent changes were validated in both yearly and daily time scales. The 24 h mean survival rate peaked in spring (92%) compared to fall (72%), the 20% difference being statistically significant (χ² test with p<0.05 and cosinor with p<0.0001 for seasonal rhythm detection and with a peak time, Ø,=April 3±6.6 days). A 24 h rhythm was also detected in each of the seasonal time points. However, the curve pattern was monophasic in fall as well as spring. In fall, a large amplitude (A) circadian rhythm was detected that peaked at 19 HALO, while in the spring, a small circadian rhythm was detected that peaked at 1 HALO. The curve pattern was biphasic in summer (with large A) and in winter (with a small A). The existence of two peaks of equal magnitude in winter (100% survival rate) and in summer (100% and 90%) suggests the presence of both circadian and ultradian rhythms rather than an ultradian component of the 24 h period. The seasonal modulation of ondansetron circadian chronotolerance seems to involve several rhythm parameters: season‐related changes in the 24 h mean (M), amplitude (A), acrophase location (Ø), as well as bimodal curve patterns including the coexistence of rhythms with respectively 24 and 8 h periods in winter and summer. In conclusion, tolerance to ondansetron varies not only according to the 24 and 8 h periods but also according to seasons, which suggests the complexity of ondansetron toxicity rhythms. Seasonal modulation of ondansetron tolerance may also influence the strategies of chemo‐and chrono‐therapy, and it is therefore necessary to take it into account in clinical drug‐delivery protocols to minimize side effects of cytotoxic anticancer and antiemetic agents.     

Chronicle of a summer and the editing of cinema‐verite

Jean Rouch and Edgar Morin's Chronicle of a Summer is held up as an innovative, seminal “work in the formation of cinéma‐vérité, and has a central position in the development of documentary and ethnographic filmmaking. Although much has been written about fthis film, little attention has been paid to the film's construction. This paper examines ‘elements of the editing structure of Chronicle of a Summer both to consider how this “work was shaped given the constraints of its production and intended reception and to ¦ analyze a relatively neglected aspect of documentary film practice.     

The group of 77 and the establishment of the international sea‐bed authority

Abstract

The Group of 77 favors the establishment of a strong International Sea‐Bed Authority with powers to regulate and control all the activities of exploration and exploitation of the “common heritage of mankind,”; referred to in the draft articles as “the Area.”; The Authority itself is to be composed of an Assembly as the supreme policy‐making organ in which the Contracting Parties are to be represented on the basis of sovereign equality; a Council as the executive organ implementing the policies emanating from the Assembly, to be composed of at least 36 states elected to ensure representation of clearly defined special interests and the principle of equitable geographical distribution, and to eschew any form of veto mechanism in its decision‐making process; the Enterprise as the operational organ through which the Authority is to undertake direct exploitation of the Area along with the other entities given access to the Area; and a Secretariat as well as certain subsidiary bodies of the Council.

The Group of 77 takes the position that the Convention itself and the Basic Conditions governing the entire process of exploration and exploitation of the Area must leave the Authority an appreciable margin of discretion in managing the Area for the benefit of mankind as a whole. Thus, a limited category of judicially reviewable decisions of the Authority is envisaged so long as such review does not challenge the legislative powers and resource policy decisions of the Authority. A Sea‐Bed Tribunal is no longer necessary as an organ of the Authority, since the work of such a Tribunal could be done by the special Sea‐Bed Disputes Chamber of the Proposed Law of the Sea Tribunal dealing with disputes arising under the Convention as a whole.     

The challenge of understanding the Asian‐American experience

Roger Daniels, ASIAN AMERICA: CHINESE AND JAPANESE IN THE UNITED STATES SINCE 1850, Seattle: University of Washington Press, 1988, 344 pp., $24.95 (hardback).

Harriet Duleep, THE ECONOMIC STATUS OF AMERICANS OF ASIAN DESCENT: AN EXPLORATORY INVESTIGATION, Washington DC: US Commission on Civil Rights Clearinghouse Publication 95, October 1988.

James A. Freeman, HEARTS OF SORROW: VIETNAMESE‐AMERICAN LIVES, Stanford, CA: Stanford University Press, 1989, 427 pp., $29.50 (hard cover)     

Administration‐Time‐Dependent Effects of Olmesartan on the Ambulatory Blood Pressure of Essential Hypertension Patients

Previous studies established that a single daily dose of olmesartan remains effective for the entire 24 h without alteration of the day‐night blood pressure (BP) pattern. On the other hand, the administration of valsartan or telmisartan at bedtime, as opposed to upon wakening, improves the sleep‐time relative BP decline toward a greater dipper pattern without loss of 24 h efficacy. Yet to be determined is whether this administration‐time‐dependent efficacy is a class‐related feature, characteristic of all angiotensin‐receptor‐blocker (ARB) medications. We studied 123 grade 1 and 2 hypertensive patients, 46.6±12.3 yrs of age, randomly assigned to receive olmesartan (20 mg/day) as a monotherapy either upon awakening or at bedtime for three months. BP was measured by ambulatory monitoring for 48 consecutive hours before and after treatment. The 24 h BP reduction was similar for both treatment times. Administration of olmesartan at bedtime, however, was significantly more efficient than morning administration in reducing the nocturnal BP mean. The sleep‐time relative BP decline was slightly reduced with olmesartan ingestion upon awakening but significantly increased with ingestion at bedtime, thus reducing the prevalence of non‐dipping from baseline by 48%. Olmesartan administration at bedtime, as opposed to in the morning, improved the awake/asleep BP ratio toward a greater dipper pattern without loss of 24 h efficacy. Nocturnal BP regulation was significantly better achieved with bedtime as compared to morning dosing of olmesartan. These effects are comparable to those previously reported for valsartan and telmisartan, thus suggesting that they may be class‐related features of ARB medications in spite of differences in their half‐life kinetics. These administration‐time‐dependent effects should be taken into account when prescribing ARB medications for treatment of essential hypertension     

Reconstruction of the shape and optics of the lenses in the abathochroal‐eyed trilobite Neocobboldia chinlinica

Until now, the structure and optics of the calcite lenses in abathochroal trilobite eyes have not been investigated. So, the relationship of the abathochroal eye to other types of trilobite eyes has remained unclear. We have reconstructed the exact shape and optics of the lenses in the eodiscid trilobite Neocobboldia chinlinica to determine the mechanism of its abathochroal eye. The distal lens surface has a convex profile, while on the proximal lens surface there is a small central bulge, resulting in an undulating profile. Due to this bulge, the curvature and refractive power of the central region of the lens are greater than those of the peripheral zone. Consequently, the lens is bifocal. However, Neocobboldia could not take advantage of this bifocal property of its tiny lenses because of the diffraction of light and the infinite depth of field in object space. For the same reason, it is also sure that the undulating lower surface of the abathochroal lens did not evolve as a Huygensian profile, correcting for spherical aberration, as suggested earlier. This undulation is a result of the presence of the central bulge, the evolutionary significance of which remains enigmatic. On the basis of our results, we have outlined an evolutionary scenario for development of the optics of the lenses in trilobite eyes.     

Structure and function of the N‐terminal domain of the human mitochondrial calcium uniporter

The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti‐/pro‐apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N‐terminal domain (NTD) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake‐1 and mitochondrial calcium uptake‐2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca²⁺ uptake in a stable MCU knockdown HeLa cell line and exerted dominant‐negative effects in the wild‐type MCU‐expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.     

Measurement of the apparent diffusion coefficient of N‐butane in soil

Measurements of in‐soil diffusion coefficients and the application of an appropriate diffusional model can allow for a more accurate prediction of soil gas concentrations and movement to locate subterranean contamination of volatile materials. The present study was undertaken to measure and evaluate the “apparent in‐soil diffusion coefficient”; for n‐butane through soil columns under non‐steady‐state conditions. The term “apparent in‐soil diffusion coefficient”; refers to a numerical coefficient that primarily describes the movement of the material by diffusion but also contains effects due to other mechanisms (e.g., adsorption and solubility).

Six test columns were evaluated at three soil porosity levels ranging from 0.30 to 0.43 and at two column temperature conditions, nominally 18°C and 7°C. Soil columns measured 25.4 cm in diameter by 84 cm in height and contained a moist sand/silt/clay mixture. The numerical range for the apparent in‐soil diffusion coefficients for n‐butane was 0.447 × 10^‐3cm²/s to 0.561 × 10^‐3cm²/s. The lower coefficient values were associated with lower soil porosity levels and cooler column conditions.     

Hormonal and neuroendocrine regulation of energy balance‐the role of leptin

A new dimension to the regulation of energy balance has come from the identification of the ob (obese) gene and its protein product, leptin. Leptin is produced primarily in white adipose tissue, but synthesis also occurs in brown fat and the placenta. Several physiological functions have been described for leptin‐the inhibition of food intake, the stimulation/maintenance of energy expenditure, as a signal of energy reserves to the reproductive system, and as a factor in haematopoiesis. The production of leptin by white fat is influenced by a number of factors, including insulin and glucocorticoids (which are stimulatory), and fasting, cold exposure and ß‐adrenoceptor agonists (which are inhibitory). A key role in the regulation of leptin production is envisaged for the sympathetic nervous system, operating through ß3‐adreno‐ceptors. The leptin receptor gene is expressed in a wide range of tissues, and several splice variants are evident. A long form variant (Ob‐Rb) with an intracellular signalling domain is found particularly in the hypothalamus. Leptin exerts its central effects through neuropeptide Y, and through the glucagon‐like peptide‐1 and melanocortin systems, but it may also interact with other neuroendocrine pathways. The role and function of the leptin system in agricultural animals has not been established, but it offers a potential new target for the manipulation of body fat.     

Toxicological screening of chemical emissions from municipal solid waste landfills. application of a predictive framework to a state‐of‐the‐art facility

A screening‐level risk assessment was used to identify chemicals of potential health concern emitted during the normal operation of an hypothetical state‐of‐the‐art municipal solid waste landfill. Data on the amount of contaminants (carcinogens, non‐carcinogenic systemic toxicants, odorous compounds, and particulate‐bound metals) were obtained from existing facilities and used to estimate ground‐level air concentrations of airborne chemicals at the point of maximum impact (property line) and at year 20 (year of maximum emissions from the landfill). Concentrations of leachate components present in the corresponding underlying aquifer were also estimated. Intakes of chemicals experienced by a series of human receptors were then computed using either single‐media or multi‐media algorithms. Carcinogens of concern were selected as those contributing to a lifetime excess cancer risk (LECR) greater than 10^‐6; for non‐carcinogenic systemic toxicants and odorous volatiles an Exposure Ratio (ER=intake or concentration/RfD, RfC, odor threshold) greater than 0.1 was used as cut‐off. The results obtained identified a final set of air emission components (n = 25) constituted mainly of carcinogenic and odorous substances whereas 2 leachate components were retained. Additional analysis using more refined risk‐based approaches are necessary to verify the relevance of these projections.     

The season‐of‐birth paradox

Abstract

Vital statistics data show a remarkably consistent seasonality in U.S. birth patterns, with peaks in late summer and winter months, and a valley in the spring. An attitude survey of college students suggests that peaks in the actual birth distribution occur in unpopular months in which to give birth; the valley in the actual birth distribution occurs in popular months. This paradoxical finding is named the Season‐of‐Birth Paradox. Explanations to resolve the paradox include biological and psychological components. A psychological mechanism—named the Misinformed Reproducer Hypothesis—is tested using NSFG data from the 1973–75 and 1979–81 cycles. Results suggest that women stop contracepting with the expectation that they will get pregnant almost immediately. When it takes several months on the average for a successful conception to occur, the actual birth distribution is shifted away from the preferred birth distribution. These results suggest that psychological as well as biological mechanisms underlie the consistent seasonality patterns in U.S. births.     

Over‐expression of the murine polymeric immunoglobulin receptor gene in the mammary gland of transgenic mice

The polymeric immunoglobulin receptor (pIgR), a transmembrane protein, transports dimeric IgA (dIgA) across the epithelial cells of the mucosal surfaces into the external secretions, for example milk from the mammary glands. The pIgR is consumed during the transcytosis of dIgA and is cleaved at the apical side of the epithelial cells, regardless of the binding to its ligand (dIgA), to form secretory component (SC). We hypothesize that the expression level of the endogenous murine pIgR gene in the epithelial cells is ratelimiting for the transport of dIgA across the epithelial cells into the secretions. We address this key issue by generating transgenic mice overexpressing the pIgR gene in their mammary glands in order to examine the effect on dIgA levels in the milk. Here we report on the generation of transgenic mice and analysis of the expression level of pIgR in their mammary glands. We cloned and characterized the murine pIgR gene and constructed an expression cassette bearing the pIgR gene under the control of the regulatory sequences of the bovine _s1casein gene. Four transgenic lines were made, expressing the pIgR construct at RNA and protein level only in their mammary glands. The levels of the SC protein in the milk ranged from 0.1 to 2.7mg/ml during midlactation. These levels are 10–270 times higher than wildtype SC levels (0.01mg/ml).