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The generation of life events in recurrent and non-recurrent depression.

BACKGROUND: The stress generation hypothesis proposed by Hammen (1991) holds that depressed individuals generate stressful conditions for themselves, which lead to recurrence. The original test of this hypothesis compared dependent life events in women with recurrent depression to medical and normal controls. Two further research questions emerged from this work: (a) do individuals with a history of many depressive episodes generate more dependent life events than depressives with fewer episodes?; and (b) what is the aetiological relevance of any stress that may be generated? METHODS: The present research tested differences in dependent and independent events between depressed individuals who had experienced: (a) no previous major depressive episodes; (b) one previous episode; and (c) two or more previous episodes. We predicted that, based on the stress generation hypothesis, recurrent depressives would show more dependent events than people without a depression history, and that these generated stressors would be of aetiological importance for precipitating recurrence (i.e. severe events in the 3 months preceding recurrence). RESULTS: Recurrent depressives experienced significantly more total dependent events than first-onset depressives in the 12 months, but not the 3 months, preceding their episode. CONCLUSIONS: Although the findings supported the general premise of stress generation, the aetiological relevance of the generated stress for recurrence requires further study.

Adult↗

Generation of triplet and cation-radical bacteriochlorophyll a in carotenoidless LH1 and LH2 antenna complexes from Rhodobacter sphaeroides.

The LH1 antenna complex and a native form of the LH2 complex were isolated from the carotenoidless R26 and R26.1 mutants of Rhodobacter sphaeroides by the use of a new detergent, sucrose monocholate. One-color, pump-and-probe transient Raman spectroscopy of these complexes using 351 nm, approximately 50 ps pulses showed the generation of the triplet state of bacteriochlorophyll a (BChl a), whereas measurements using 355 nm, approximately 12 ns pulses showed the generation of BChl a cation radical. Subpicosecond to nanosecond time-resolved absorption spectroscopy using 388 nm, 200 fs pulses for excitation showed rapid (<1 ps) generation of the triplet state and fast decay (<10 ps) of the singlet state of BChl a. Microsecond absorption spectroscopy confirmed the generation of BChl a cation radical. EPR spectroscopy using 532 nm, approximately 5 ns pulses for excitation established the generation of BChl a cation radical. The EPR line width suggested that the unpaired electron is shared by two BChl a molecules. In LH1, the yield of BChl a cation radical per complex was estimated to be about 80% of that in the reaction center, and in LH2 about 50%. Thus, rapid generation of the triplet state, and its subsequent transformation into the cation-radical state of BChl a have been shown to be intrinsic properties of B870 and B850 BChl a assembly in the carotenoidless LH1 and LH2 antenna complexes. In the case of the carotenoid-containing LH2 complex, the triplet states of BChl a and carotenoid (spheroidene) were generated immediately after excitation, but the triplet-state BChl a was quenched efficiently by the carotenoid so that no BChl a cation radical was generated. Thus, the photoprotective function of the carotenoid in this antenna complex is shown.

Bacterial Proteins↗

Procedure for determining maximum sustainable power generated by microbial fuel cells.

Power generated by microbial fuel cells is computed as a product of current passing through an external resistor and voltage drop across this resistor. If the applied resistance is very low, then high instantaneous power generated by the cell is measured, which is not sustainable; the cell cannot deliver that much power for long periods of time. Since using small electrical resistors leads to erroneous assessment of the capabilities of microbial fuel cells, a question arises: what resistor should be used in such measurements? To address this question, we have defined the sustainable power as the steady state of power delivery by a microbial fuel cell under a given set of conditions and the maximum sustainable power as the highest sustainable power that a microbial fuel cell can deliver under a given set of conditions. Selecting the external resistance that is associated with the maximum sustainable power in a microbial fuel cell (MFC) is difficult because the operator has limited influence on the main factors that control power generation: the rate of charge transfer at the current-limiting electrode and the potential established across the fuel cell. The internal electrical resistance of microbial fuel cells varies, and it depends on the operational conditions of the fuel cell. We have designed an empirical procedure to predict the maximum sustainable power that can be generated by a microbial fuel cell operated under a given set of conditions. Following the procedure, we change the external resistors incrementally, in steps of 500 omega every 10, 60, or 180 s and measure the anode potential, the cathode potential, and the cell current. Power generated in the microbial fuel cell that we were using was limited by the anodic current. The anodic potential was used to determine the condition where the maximum sustainable power is obtained. The procedure is simple, microbial fuel cells can be characterized within an hour, and the results of the measurements can serve many purposes, such as: (1) estimating power generation in various MFCs, (2) comparing power generation in MFCs using different electroactive reactants, (3) quantifying the effects of the operational regime on the power generation in MFCs, and finally, (4) the purpose for which the procedure was designed, optimizing the performance of existing MFCs.

Bacteria↗

Generation of free radicals from model lipid hydroperoxides and H2O2 by Co(II) in the presence of cysteinyl and histidyl chelators.

Electron spin resonance spin trapping was utilized to investigate the generation of free radicals from cumene hydroperoxide (cumene-OOH), tert-butyl hydroperoxide (tert-butyl-OOH), and H2O2 at pH 7.2 by Co(II) in the presence of cysteinyl and histidyl chelating agents. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide. Incubation of Co(II) with cumene-OOH or tert-butyl-OOH did not generate any detectable amounts of free radicals. However, in the presence of glutathione, cysteine, penicillamine, or N-acetylcysteine, Co(II) generated cumene-OOH-derived carbon-centered radicals, cumene alkoxyl radicals, and hydroxyl (.OH) radicals. Oxidized glutathione and cystine used instead of reduced glutathione or cysteine did not generate any free radical, indicating an important role of the -SH group in radical generation. While the addition of diethylenetriaminepentaacetic acid (DTPA) prevented radical generation, deferoxamine had only a slightly inhibitory effect. Similar results to those obtained using cumene-OOH were obtained utilizing tert-butyl-OOH in place of cumene-OOH. The yields of free radicals were in the order of glutathione > cysteine > penicillamine > N-acetylcysteine. Incubation of Co(II) with cumene-OOH ort-butyl-OOH in the presence of the histidyl oligopeptide Gly-Gly-His also generated lipid hydroperoxide-derived free radicals, with the yield being comparable to that obtained using thiols. In contrast, histidine, anserine, homocarnosine, or carnosine did not cause any free radical generation from Co(II) and lipid hydroperoxides. Incubation of Co(II) with H2)2 produced only a small amount of .OH radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

Troponin C regulates the rate constant for the dissociation of force-generating myosin cross-bridges in cardiac muscle.

It is well known that cardiac troponin C (cTnC) regulates the association of force-generating myosin cross-bridges. We report here evidence for an additional role for cTnC. This hypothesis states that Ca2+ binds more strongly to cTnC when force-generating myosin cross-bridges are attached to actin and that removal of this bound Ca2+ accelerates the dissociation of force-generating myosin cross-bridges. Intact Fura-2-loaded rat papillary muscles and skinned (permeabilized) ventricular preparations were used. The preparations were mounted in the Guth Muscle Research System which is capable of measuring simultaneously fluorescence and force in response to length perturbations. All mechanical perturbations of muscle length (isotonic shortening, quick stretches and releases, and length vibrations) which cause dissociation of force-generating myosin cross-bridges during a twitch resulted in Ca2+ being released from troponin as judged from changes in the Ca2+ transients (Fura-2 (340/380) fluorescence ratio). Thus dissociation of force-generating myosin cross-bridges cause Ca2+ to be released from cTnC. Conversely, it would be expected that removal of strongly bound Ca2+ from cTnC would result in an increase in the rate of dissociation of force-generating myosin cross-bridges. To test this hypothesis actomyosin ATPase (NADH fluorescence change) and isometric force were measured in skinned cardiac preparations. The ratio of the ATPase/Force is proportional to the rate constant (gapp) for the dissociation of force-generating myosin cross-bridges. The data showed that decreasing the amount of Ca2+ bound to cTnC in skinned cardiac fibers caused an increase in the ratio of ATPase/Force, the rate of dissociation (gapp) of force-generating myosin cross-bridges.

Animals↗

Effects of occlusiveness of a titanium cap on bone generation beyond the skeletal envelope in the rabbit calvarium.

We evaluate the effects of occlusiveness of a titanium cap on bone generation beyond the skeletal envelope. In eight rabbits, the calvarial bone was exposed and a circular groove was prepared with a trephine drill. After marrow penetration, a standardized hemispherical titanium cap, either with or without small holes (1.5 mm in diameter), was then placed into the bone and covered by a cutaneous flap. After 1 month or 3 months of healing, the animals were euthanized and examined histologically. The percentage area of newly generated tissue consisting of mineralized bone and marrow spaces in each section was calculated relative to the area bounded by the hemispherical shape of the titanium cap and the parent bone; this latter volume was taken to be 100%. Furthermore, the cross-sectional areas of generated mineralized bone expressed as percentages of the total tissue area generated within each space were determined. In the 1-month specimens, there was no statistically significant difference between the two caps in the amount of tissue generated, 54.7%+/-12.2% with holes vs. 60.4%+/-8.8% without holes (p=0.225). However, in the 3-month specimens, we observed a significant difference between the caps (55.9%+/-7.4% with holes vs. 89.9%+/-6.5% without holes, P<0.05). Also, there was a statistically significant difference between 1- and 3-month specimens in the amount of tissue generated under the cap without holes (60.4%+/-8.8% vs. 89.9%+/-6.5%, P<0.05). Although there was no significant difference in the relative amount of mineralized bone generated between the caps with holes and those without holes in the 1-month specimens (27.7%+/-4.8% vs. 30.8%+/-6.4%, P=0.225), there was a statistically significant difference between the two caps in the 3-month specimens (24.3%+/-4.1% with holes vs. 34.0%+/-8.6% without holes, P<0.05). A substantial ingrowth of fibrous connective tissue through the holes appeared to prevent further new tissue generation in a defined area adjacent to the bone surface. We concluded that total occlusiveness, sufficient stiffness of the cap, as well as the passage of time will allow predictable mineralized bone augmentation to occur in spaces beyond the skeletal envelope.

Animals↗

Generativity among young, midlife, and older adults.

Generativity is conceived as a configuration of psychosocial features constellated around the goal of providing for the next generation. This study used a stratified random sampling of young (ages 22-27), midlife (ages 37-42), and older (ages 67-72) adults to examine age-cohort differences in 4 generativity features: generative concern, commitments, actions, and narration. Although prevailing views on generativity (e.g., Erikson, 1963) predict a peak in midlife and decline thereafter, support for this developmental hypothesis was mixed. Midlife Ss scored higher than young and older Ss on concern and actions in a second administration of measures, but not in the first. Generative commitments and narration showed high scores for both midlife and older Ss and relatively low scores for young Ss. Generative concern, assessed with the Loyola Generativity Scale, was positively associated with life satisfaction.

Activities of Daily Living↗

Generation and hypermnesia.

The multifactor account of the generation effect makes detailed predictions about the effects of generation on item-specific and relational encoding, predictions confirmed in four experiments using a multiple-test methodology. In pure-list designs with unrelated study items, generation produced more interest item gains (indexing greater item-specific processing) and more interest item losses (indexing less relational processing) relative to the read condition. In a mixed-list design, generation produced more gains but did not affect losses. With categorically-related study items, generation produced more gains but fewer losses (indicating enhanced relational encoding). Generation consistently produced hypermnesia whereas reading did so only for related study items. Also, a significant generation effect emerged on later tests under conditions (between-subjects design, unrelated study items) which typically yield no generation effect.

Adult↗

When does generation enhance memory for location?

Generation is thought to enhance both item-specific and relational processing of generated targets as compared with read words (M. A. McDaniel & P. J. Waddill, 1990). Generation facilitates encoding of the cue-target relation and sometimes boosts encoding of relations across list items. Of interest is whether generation can also increase the encoding of target-location associations. Because the literature on this point is mixed, 3 procedural differences between 2 studies (E. J. Marsh, G. Edelman, & G. H. Bower, 2001; N. W. Mulligan, 2004) were identified and manipulated. A positive generation effect was found for location memory, but this effect was reduced when subjects wrote down the study words and when the filler task involved generation. Generation can enhance location memory in addition to item memory but only if the experimental parameters do not interfere with the processing benefits of generation.

Cues↗

Generation of ultraviolet entangled photons in a semiconductor.

Entanglement is one of the key features of quantum information and communications technology. The method that has been used most frequently to generate highly entangled pairs of photons is parametric down-conversion. Short-wavelength entangled photons are desirable for generating further entanglement between three or four photons, but it is difficult to use parametric down-conversion to generate suitably energetic entangled photon pairs. One method that is expected to be applicable for the generation of such photons is resonant hyper-parametric scattering (RHPS): a pair of entangled photons is generated in a semiconductor via an electronically resonant third-order nonlinear optical process. Semiconductor-based sources of entangled photons would also be advantageous for practical quantum technologies, but attempts to generate entangled photons in semiconductors have not yet been successful. Here we report experimental evidence for the generation of ultraviolet entangled photon pairs by means of biexciton resonant RHPS in a single crystal of the semiconductor CuCl. We anticipate that our results will open the way to the generation of entangled photons by current injection, analogous to current-driven single photon sources.

Journal Article↗

Anticipation in familial intracranial aneurysms in consecutive generations.

Intracranial aneurysms (IA) are the major cause of subarachnoid haemorrhages (SAH). A positive family history for SAH is reported in 5-10% of the patients. The mode of inheritance is not unambiguously established; both autosomal dominant and recessive modes have been reported. In sporadic as well as in familial SAH, approximately 60% of the SAH patients are female. Recently, anticipation has been described in familial SAH. Since up to 15% of the SAHs are not caused by an IA, we have analysed anticipation, sex ratio and mode of inheritance only in families with patients with a proven IA in two consecutive generations. A total of 10 families were studied in which at least two persons in consecutive generations were affected by SAH, a symptomatic IA (SIA) or a presymptomatic IA (PIA). We also analysed published data from families with a proven IA in two consecutive generations on age of SIA onset and sex ratios among affected family members (both SIA and PIA). The age of SIA onset in the parental generation (mean 55.5 years) differed significantly from the age of onset in their children (mean 32.4 years). In the parental generation 11 men and 37 women were affected (both SIA and PIA), in the consecutive generation these numbers were 28 men and 32 women. There is a significant difference in sex ratio of affected family members when the generations are compared (P<0.02). No family could be found in which three consecutive generations were affected by an IA (SIA or PIA).

Adult↗

'Advanced' generation lentiviruses as efficient vectors for cardiomyocyte gene transduction in vitro and in vivo.

Efficient gene transduction in cardiomyocytes is a task that can be accomplished only by viral vectors. Up to now, the most commonly used vectors for this purpose have been adenoviral-derived ones. Recently, it has been demonstrated that lentiviral vectors can transduce growth-arrested cells, such as hematopoietic stem cells. Moreover, a modified form of lentiviral vector (the 'advanced' generation), containing an mRNA-stabilizer sequence and a nuclear import sequence, has been shown to significantly improve gene transduction in growth-arrested cells as compared to the third-generation vector. Therefore, we tested whether the 'advanced' generation lentivirus is capable of infecting and transducing cardiomyocytes both in vitro and in vivo, comparing efficacy in vitro against the third-generation of the same vector. Here we report that 'advanced' generation lentiviral vectors infected most (>80%) cardiomyocytes in culture, as demonstrated by immunofluorescence and FACS analyses: in contrast the percentage of cardiomyocytes infected by third-generation lentivirus was three- to four-fold lower. Moreover, 'advanced' generation lentivirus was also capable of infecting and inducing stable gene expression in adult myocardium in vivo. Thus, 'advanced' generation lentiviral vectors can be used for both in vitro and in vivo gene expression studies in the cardiomyocyte.

Animals↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Alcohol-related disorders in first- and second-generation immigrants in Sweden: a national cohort study.

AIMS: The risk of alcohol-related disorders in first- and second-generation immigrants in Sweden were investigated and compared with the Swedish majority population to assess how alcohol habits are modified over generations in a new society. DESIGN: Register study based on multivariate analyses of demographic data, including information on country of birth, from the Swedish Population and Housing Census of 1985 linked to data on hospital admissions for alcohol-related disorders during 1990-99 in the National Hospital Discharge Register. PARTICIPANTS: The study population consisted of a national cohort of 1.25 million youth born 1968-79 and 1.47 million adults born 1929-65. RESULTS: First- and second-generation immigrants from Finland had higher relative risks (RRs) for hospital admission because of an alcohol-related disorder compared to the Swedish majority population (socio-economic adjusted RRs 2.1 and 1.9, respectively), while first-generation immigrants born in southern Europe, the Middle East and other non-European countries had lower risks. Second-generation immigrants with heritage in southern Europe, the Middle East and other non-European countries had socio-economic adjusted RRs that were higher relative to the first generation immigrants but lower relative to the Swedish majority population. Intercountry adoptees had the highest adjusted RR (2.5). CONCLUSIONS: Patterns of alcohol abuse in the country of origin are strong determinants of alcohol-related disorders in first-generation immigrants. The patterns in second-generation immigrants are influenced by parental countries of origin as well as patterns in the majority population. The Finnish minority and intercountry adoptees are of particular concern in prevention.

Adult↗

Generation of reactive oxygen species is not involved in idarubicin-induced apoptosis in human leukaemic cells.

The anthracycline antibiotic idarubicin (IDA) induces double-stranded DNA breaks, the generation of reactive oxygen species (ROS) and apoptosis in human leukaemic cells. It is unclear whether the generation of ROS is associated with the apoptotic process. Using the T-lymphoblastic leukaemic CEM cell line, we found that IDA-induced DNA breaks were correlated with final cell death. The reduction in mitochondrial membrane potential (Deltapsim) and the generation of ROS occurred simultaneously with IDA-induced activation of caspase-9 and caspase-3. Inhibition of caspases by a pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk) completely blocked IDA-induced reduction of Deltapsim, apoptosis and final cell death. Interestingly, ROS generation was significantly enhanced by Z-VAD-fmk. ROS generation was neither caspase dependent nor part of the apoptotic process. IDA-mediated reduction in Deltapsim is caspase dependent and is not a consequence of the generation of ROS. These results indicate that IDA-induced generation of ROS and apoptosis are separate events. Inhibition of caspases facilitates IDA-mediated generation of ROS.

Amino Acid Chloromethyl Ketones↗

NMDA receptor activation produces concurrent generation of nitric oxide and reactive oxygen species: implication for cell death.

The ability of glutamate to stimulate generation of intracellular oxidant species was determined by microfluorescence in cerebellar granule cells loaded with the oxidant-sensitive fluorescent dye 2,7-dichlorofluorescin (DCF). Exposure of cells to glutamate (10 microM) produced a rapid generation of oxidants that was blocked approximately 70% by MK-801 (a noncompetitive NMDA-receptor antagonist). To determine if nitric oxide (NO) or reactive oxygen species (ROS) contributed to the oxidation of DCF, cells were treated with compounds that altered their generation. NO production was inhibited with NG-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) and reduced hemoglobin (NO scavenger). Alternatively, cells were incubated with superoxide dismutase (SOD) and catalase, which selectively metabolize O2-. and H2O2. Concurrent inhibition of O2-. and NO production nearly abolished intracellular oxidant generation. Pretreatment of cells with either chelerythrine (1 microM, protein kinase C inhibitor) or quinacrine (5 microM, phospholipase A2 inhibitor) before addition of glutamate also blocked oxidation of DCF. Generation of oxidants by glutamate was significantly reduced by incubating the cells of Ca(2+)-free buffer. In cytotoxicity studies, a positive correlation was observed between glutamate-induced death and oxidant generation. Glutamate-induced cytotoxicity was blocked by MK-801 and attenuated by treatment with L-NAME, chelerythrine, SOD, or quinacrine. It is concluded that glutamate induces concurrent generation of NO and ROS by activation of both NMDA receptors and non-NMDA receptors through a Ca(2+)-mediated process. Activation of NO synthase and phospholipase A2 contribute significantly to this response. It is proposed that simultaneous generation of NO and ROS results in formation of peroxynitrite, which initiates the cellular damage.

Animals↗

Phosphorylation of extracellular-regulating kinase in NMDA receptor antagonist-induced newly generated neurons in the adult rat dentate gyrus.

Neurogenesis in the adult brain is promoted by various stimulations. NMDA receptor blockade enhances neurogenesis in the hippocampal dentate gyrus. There is no agreed conclusion, however, as to whether newly generated neurons after NMDA receptor blockade obtain functional properties. We investigated the functional maturation of newly generated neurons after NMDA receptor blockade. In the dentate gyrus, 80% of newly generated cells differentiated into the phenotype of mature neurons at 29 days after the single intraperitoneal injection of an NMDA receptor antagonist MK-801. The number of newly generated neurons after MK-801 treatment was significantly greater than that in the saline-treated group. The neurogenic basic helix-loop-helix transcription factor NeuroD protein in the dentate gyrus after MK-801 treatment was expressed transiently in proliferative cells, but not in mature neurons. To determine functional properties of newly generated neurons, we administered NMDA to the lateral ventricle. As an in vivo response, we assessed extracellular-regulating kinase (ERK) phosphorylation. The newly generated neurons showed ERK phosphorylation by NMDA administration as seen in surrounding mature neurons. The number of newly generated neurons, which responded to NMDA receptor stimulation, increased with time after MK-801 treatment. The present study provides evidence that newly generated neurons in the adult hippocampus after NMDA receptor blockade acquire biochemical function in vivo.

Animals↗

Prospective assessment of donor blood screening for antibody to hepatitis C virus by first- and second-generation assays as a means of preventing posttransfusion hepatitis.

In November 1989, the Japanese Red Cross began screening blood donors for the hepatitis C virus antibody (anti-HCV) by first-generation assay and high-titer hepatitis B virus core antigen antibody. A significant reduction in the incidence of acute posttransfusion hepatitis was reported; however, the incidence still ranged from 2 percent to 4 percent. The Red Cross changed to the second-generation assay in February 1992, the objective being the complete elimination of potential posttransfusion hepatitis. The aim was to elucidate the advantage of second-generation assay as a blood-donor screening test. The incidence of posttransfusion hepatitis after the introduction of second-generation assay was compared with that before the introduction of the first-generation assay and with that during its use. The incidence of posttransfusion hepatitis was 9.6 percent (216/2,240) before anti-HCV-s donor screening. It was 3.7 percent (24/655) and 0.9 percent (3/326) after the introductions of the first- and second-generation hepatitis C virus (HCV) assays, respectively (chi (2) = 50.0, P < .01). Blood-donor screening by second-generation anti-HCV provided a significant benefit compared with the first-generation assay.

Adult↗