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The article discusses the potential of genomics in archaeological research and highlights the advances made in the field due to genetics. It mentions the peopling of Polynesia and the discovery that South Americans populated some of the easternmost Polynesian islands around the same time as Polynesians arrived from the west. The article also mentions the interest in mapping the genome of the Americas to trace the migration routes of Native Americans. The editors recommend a comprehensive book on the topic titled "Origin: A Genetic History of the Americas" by Jennifer Raff. [Extracted from the article]

When it comes to selecting cryogenic piping, cost is always a driving factor. But, the system with the cheapest initial expenditure is not necessarily the most economical solution. Calculating the [...]

There have been no trials of task-shared care (TSC) using WHO's mental health Gap Action Programme for people with severe mental disorders (psychosis or affective disorder) in low-income or middle-income countries. We aimed to evaluate the efficacy and cost-effectiveness of TSC compared with enhanced specialist mental health care in rural Ethiopia.

It is common to see patients with both alcohol problems and psychiatric symptoms, but the long-term consequences of alcohol consumption on mental health have not been addressed in the literature. It is also difficult to study the relationship between alcohol consumption and psychiatric illness because the effects of current alcohol abuse are sometimes hard to distinguish from psychiatric symptoms. Whether or not alcohol contributes to dementia is another issue of debate. Although a number of studies have found that cognitive changes are associated with heavy alcohol use, many argue that the changes reverse with abstinence. In the present study, data from a three-year longitudinal survey were gathered for 1,070 subjects aged 65 years and over. At three-year follow-up, 701 of the subjects were re-interviewed. Of the men in the sample, 9 percent had a history of heavy drinking, and 0.5 percent of women had a history of heavy drinking. Only the men were used for further analysis because of the small number of women with a history of heavy drinking. Forty-four percent of those with histories of heavy drinking were given a psychiatric diagnosis, mostly depression, compared with 12 percent of men with no such history. Sixteen percent of heavy drinkers showed signs of dementia compared with only 3.9 percent of men without a history of heavy drinking. Controlling for current drinking habits, the relationship still held. Heavy alcohol consumption earlier in life was associated with the development of psychiatric illness in the men in this study. (Consumer Summary produced by Reliance Medical Information, Inc.)

Without publication research can be of little value. When researchers approach publication there is ample published guidance for them on what their obligations are, and there are well known style [...]

Neighbourhood social context might play a role in modifying mortality outcomes in severe mental illness, but has received little attention to date. Therefore, we aimed to assess in an ethnically diverse and urban location the association of neighbourhood-level characteristics and individual-level factors for all-cause, natural-cause, and unnatural-cause mortality in those with severe mental illness.

Abstract Objective To evaluate the effectiveness of home visiting programmes that offer health promotion and preventive care to older people. Design Systematic review and meta-analysis of 15 studies of home [...]

Authors' conclusions were not justified by findings EDITOR--In their randomised trial of antidepressant drugs and generic counselling for treating depression, Chilvers et al concluded that generic counselling is as effective [...]

Abstract Objectives To compare the efficacy of antidepressant drugs and generic counselling for treating mild to moderate depression in general practice. To determine whether the outcomes were similar for patients [...]

This was my first find. I was just starting off and getting my interest in antiques and collectibles. I didn't want to do it full time but I wanted to [...]

Deer mice (Peromyscus) are the most common native North American mammals, and exhibit great natural genetic variation. Wild‐derived stocks from a number of populations are available from the PeromyscusGenetic Stock Center (PGSC). The PGSCalso houses a number of natural variants and mutants (many of which appear to differ from Mus). These include metabolic, coat‐color/pattern, neurological, and other morphological variants/mutants. Nearly all these mutants are on a common genetic background, the Peromyscus maniculatusBWstock. Peromyscusare also superior behavior models in areas such as repetitive behavior and pair‐bonding effects, as multiple species are monogamous. While Peromyscusdevelopment generally resembles that of Musand Rattus, prenatal stages have not been as thoroughly studied, and there appear to be intriguing differences (e.g., longer time spent at the two‐cell stage). Development is greatly perturbed in crosses between P. maniculatus(BW) and Peromyscus polionotus(PO). BWfemales crossed to POmales produce growth‐restricted, but otherwise healthy, fertile offspring which allows for genetic analyses of the many traits that differ between these two species. POfemales crossed to BWmales produce overgrown but severely dysmorphic conceptuses that rarely survive to late gestation. There are likely many more uses for these animals as developmental models than we have described here. Peromyscusmodels can now be more fully exploited due to the emerging genetic (full linkage map), genomic (genomes of four stocks have been sequenced) and reproductive resources. This article is categorized under: Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and TimingNervous System Development > Vertebrates: General PrinciplesComparative Development and Evolution > Model Systems

Peromyscus spp. are the most abundant native North American mammals. They have gained popularity as research animals in the last 20 years, and this trend is expected to continue as new research tools, such as whole genome sequences, baseline physiological data and others, become available. Concurrently, advances have been made in the recommendations for the care of laboratory animals. The authors provide insight into how the Peromyscus Genetic Stock Center successfully breeds and maintains several stocks of deer mice and related species. This information is beneficial to researchers that plan to include Peromyscus spp. in their research programs.

To investigate inpatient mortality and the use of invasive diagnostic and revascularization procedures after acute myocardial infarction (AMI) in people with schizophrenia and bipolar disorder.

Results of the few cohort studies from countries with low incomes or middle incomes suggest a lower incidence of dementia than in high-income countries. We assessed incidence of dementia according to criteria from the 10/66 Dementia Research Group and Diagnostic and Statistical Manual of Mental Disorders (DSM) IV, the effect of dementia at baseline on mortality, and the independent effects of age, sex, socioeconomic position, and indicators of cognitive reserve.

To investigate changes over 15 years in the prevalence of insomnia and its association with demographic characteristics and hypnotic medication use.

Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo.

Complications after stroke have been shown to impede rehabilitation, lead to poor functional outcome, and increase cost of care. This inception cohort study sought to investigate the prevalence of immobility-related complications during the first year after severely disabling stroke in relation to functional independence and place of residence.

Elevated glucose levels in the presence of insulin are indicative of type 2 diabetes and the more inclusive metabolic syndrome. Alleles conferring susceptibility to these and other common conditions may be adaptations to past environments. It is possible that other mammals exhibiting environmental diversity harbor similar variants; therefore, we assessed glucose regulation in two species of deer mice (Peromyscus), a diverse endemic North American group. The prairie deer mouse, P. maniculatus bairdii (BW), and the Oldfield mouse, P. polionotus subgriseus (PO) differ in sexual dimorphism, behavior and habitat. PO animals exhibit better regulatory ability than BW animals, particularly among males, although both species display equivalent insulin levels/responses and non-fasted glucose levels. Hybrid males exhibit a PO glucose challenge response and subsequent analysis of consomic animals implicates Y chromosome variation as the genetic cause. Two pieces of evidence indicate that the male glucose regulatory differences are mediated by stress response: (1) fasting and handling alone account for most of the variation; (2) an inhibitor of glucocorticoid (GC) stress hormone synthesis eliminates these differences. PO males have GC levels that are twice those of BW males, indicating the presence of alleles that attenuate the GC response. We hypothesize that the interspecific physiological and behavioral differences are interrelated and that similar human variants exist.

To investigate empirically the association between anxiety/depression and cause-specific mortality with particular attention to the underlying mechanisms and causes of death. Depression reportedly increases general mortality. For cause-specific mortality, there is evidence depression has an effect on cardiovascular disease (CVD) mortality and suicide. Less information is known as to other mortality diagnoses. There is scarce and conflicting literature on anxiety in relation to mortality.

Associations between disability and depression have been shown to be consistent across cultures among middle-aged adults. In later life the association between disability and depression is much more substantial and may be amenable to influences by health care facilities as well as economic and sociocultural factors. Fourteen community-based studies on depression in later life in 11 western European countries contribute to a total study sample of 22,570 respondents aged 65 years or older. Measures are harmonised for depressive symptoms (EURO-D scale) and disability. Using multilevel modelling to control for the stratified data structure we examined whether the association between disability and depressive symptoms is modified by national health care and mental health care availability, national economic circumstances, demographic characteristics and religious tradition. The association between depressive symptoms and disability is attenuated by health care expenditure and availability of mental health care and also by gross domestic product; it was more pronounced in countries with high levels of orthodox religious beliefs. Higher levels of depressive symptoms are found in countries with a larger gross domestic product (per capita) and higher health care expenses but are interpreted with care because of measurement differences between the centres. The findings from this contextual perspective indicate that general and mental health care should be geared to one another wherever possible.

An investigation was initiated to explore previously published results indicating that ∼80 bp of the 5′-end of the iduronate sulfatase (IDS) cDNA sequence (Accession No L07291) are 100% homologous with the 3′-UTR of isoform 1 of the sodium hydrogen exchanger (Acc. No. U51112). 5′-RACE carried out on IDS mRNA demonstrated the apparent homology to be a cloning artifact. A sequence comparison of the IDS 5′-RACE product with a mouse BAC clone covering the region, and with various IDS ESTs, suggested that the region is highly susceptible to cloning artifacts, a common one of which is template switching by reverse transcriptase. The nucleotide sequence flanking the translation start site is unusual in containing two inverted repeats composed of the complementary trinucleotide microsatellites, (GCG)9and (CGC)6. These likely form a highly stable stem of 20–21 nt, through which reverse transcription is compromised. Such a stem could be involved in the regulation of IDS expression by directly affecting translation, message turnover, or serving as a substrate for siRNA production. Though such mRNA features are relatively rare, they may be more abundant but overlooked due to difficulties in their reverse transcription.

Populations of paddlefish Polyodon spathulahave been adversely affected by dams that can block their movements. Unlike high-head dams that preclude fish passage (unless they are equipped with fishways), the dams on the upper Mississippi River are typically low-head dams with bottom release gates that may allow fish passage under certain conditions. We evaluated the relation of dam head and river discharge to the passage of radio-tagged paddlefish through dams in the upper Mississippi River. Radio transmitters were surgically implanted into 71 paddlefish from Navigation Pools 5A and 8 of the upper Mississippi River and from two tributary rivers during fall 1994 through fall 1996. We tracked paddlefish through September 1997 and documented 53 passages through dams, 20 upstream and 33 downstream. Passages occurred mostly during spring (71%) but also occurred sporadically during summer and fall (29%). Spring passages varied among years in response to hydrologic conditions. We evaluated patterns in upstream and downstream passages with Cox proportional hazard regression models. Model results indicated that dam head height strongly affected the upstream passage of paddlefish but not the downstream passage. Several paddlefish, however, passed upstream through a dam during periods when the minimum head at the dam was substantial (=1 m). In these cases, we hypothesize that paddlefish moved upstream through the lock chamber.

We used radio telemetry to evaluate the movement and habitat use of paddlefish Polyodon spathulain the upper Mississippi River and two tributary rivers. Radio transmitters were surgically implanted into 71 paddlefish in Navigation Pools 5A and 8 of the upper Mississippi River, the Chippewa River, and the Wisconsin River during fall 1994 through fall 1996. Radio-tagged paddlefish were located through summer 1997. The range of paddlefish movement was typically low during all seasons except spring, but some paddlefish moved throughout the 420-km extent of the study area. Paddlefish tagged in the Chippewa River were closely linked with the upper Mississippi River, as substantial portions of the population inhabited the adjacent Navigation Pool 4 each spring; paddlefish in the Wisconsin River, however, rarely ventured out of that tributary. The use of aquatic area types by paddlefish varied among the study reaches. A cartographic model of paddlefish habitat suitability was developed for Navigation Pool 8 based on geographic information systems (GIS) coverages of bathymetry and current velocity. The value of paddlefish habitat in the cartographic model increased with depth and decreased with current velocity. For example, areas modeled as excellent corresponded to regions classified as having both deep water (=6.0 m) and negligible (<5 cm/s) current velocities. Our study suggests that aquatic area types are an inadequate basis for making sound management decisions regarding the critical habitats of paddlefish in complex riverine systems because such strata rely on gross geomorpological features rather than on the physicochemical variables that fish use to choose habitats. The development of systemic GIS coverages of such variables could improve the understanding of fish habitat selection and management in the upper Mississippi River.

We describe polymerase chain reaction (PCR) primers and conditions to amplify 11 microsatellite DNA loci isolated from the oldfield mouse (Peromyscus polionotus subgriseus). These were tested for amplification using nine species and subspecies maintained at the Peromyscus Genetic Stock Center, with an average success rate of 65% and two loci amplifying in all species. Polymorphism was tested within the P. polionotus subgriseus and the recently obtained P. maniculatus sonorensis colonies. P. p. subgriseus had modest numbers of alleles per locus (1–4), whereas P. m. sonorensis had many alleles per locus (5–10) and high expected heterozygosities (0.625–0.878).

Lake sturgeon Acipenser fluvescens, which are now protected from harvest, are considered rare in the upper Mississippi River and little information is available on the remaining populations. Transmitters were implanted into 31 lake sturgeon from two sites in the upper Mississippi River to describe their habitats and movement. The areas surrounding the tagging sites were core areas for both groups of lake sturgeon based on the high use (about 50% of locations by group) and frequent return to these areas by many of the tagged fish. Core areas contained sites with unique hydraulic characteristics, such that depositional substrates were common yet flow was present; these areas probably provide important feeding habitat for lake sturgeon. Minimal geographical overlap in range occurred between groups, suggesting that river reaches and associated core areas were unique to groups or substocks of fish. Lake sturgeon exhibited complex movement behaviors and had ranges of 3-198 km (median, 56 km) during the study. Tagged fish moved both downstream and upstream through upper Mississippi River navigation dams. However, dams appeared to be intermittent barriers to upstream passage because upstream passage events (10 fish, 19 passages) were fewer than downstream events (13 fish, 35 passages). Extensive use of the Wisconsin River by one group of lake sturgeon tagged in the upper Mississippi River has implications regarding management of a threatened population that transcends regulatory boundaries. Our study indicates that lake sturgeon in the upper Mississippi River system share many movement and habitat use characteristics with populations in other systems. However, significant data gaps preclude development of cogent management strategies, including information on population numbers and dynamics, identification of spawning areas, relations between groups, and assessment of the effects of commercial navigation.

A cDNA for the Mus musculusNa/H exchanger-isoform 1 (NHE-1) was identified in a BALB/c myoblast library by its hybridization to rat NHE-1 sequences. Analysis of the clone showed it to display extensive homology with NHE-1 clones from other mammalian species; however, the region of interspecific homology was abruptly interrupted in the midst of the open reading frame by 166 bp of unrelated sequence. This extra sequence is likely to be an unspliced intron 9. Aside from the retained intron 9, the NHE-1 cDNA clone is otherwise fully processed, with all of the other ten introns removed and containing a poly(A) tract. From PCR results this variant represents a significant but minor population of NHE-1 RNAs. The variant message does associate with polysomes thereby suggesting it to be translated into protein. The location of the retained intron in the carboxy terminus of the protein is such that its translation would produce a protein predicted to be still capable of effecting Na and H translocation but whose regulatory features would be markedly altered. Amino acid sequence comparison of the mouse NHE-1 (derived from the fully processed message) with that of other mammalian species demonstrated two exceptionally divergent regions; the C-terminal cytoplasmic tail (residues 750-790), containing a region of 6-8 contiguous acidic amino acids variably composed of aspartate and glutamate residues, and the N-terminal extracellular domain that includes an N-linked glycosylation site (residues 60-80).

Expression of the diphtheria toxin A-chain gene was directed to the male germ line by fusion to 1 kilobase of the 5′-flanking DNA of the rat histone H1tgene. Two independent lines of mice were established that expressed the toxic transgene. Female carriers were fertile; males were sterile although otherwise apparently normal. Adult transgenic males had very small testes that were virtually devoid of germ cells. A developmental study showed that germ cells survived until late fetal life but that testes of 3-day-old transgenic mice were severely depleted of prospermatogonia. During postnatal development of transgenic animals, remaining germ cells progressed to the pachytene stage of meiosis in 10% to 30% of tubular cross sections but degenerated before the completion of meiosis. By 3 mo of age the residual germ cells had almost completely disappeared. These transgenic lines demonstrate the complete tissue specificity of the H1tpromoter and reveal a period of its activity just prior to formation of the definitive adult spermatogonial stem cell population. Whereas full expression of H1toccurs only in mid to late pachytene spermatocytes, one or more of the factors that impart tissue specificity to its expression must be transiently activated in the neonatal germ line. This report discusses the possibility that this genetic technique for eliminating germ cells may have practical application in making recipients for spermatogonial stem cell transplantation.

We studied diel movement and habitat use by paddlefish Polyodon spathula implanted with radio transmitters in Navigation Pool 8 of the upper Mississippi River. We radio-tracked five paddlefish during three randomly chosen 24-h periods each month in May, Aug, and Oct 1995. Paddlefish were located by boat one to three times every 3 h during each 24-h period. At each location, geographic coordinates were determined with a global positioning system receiver using the Precise Positioning Service, and depth was measured with a depth sounder. Location coordinates were plotted with ARC/INFO software on a Geographic Information System land–water coverage. Movement distances were calculated as the linear distance between sequential locations. Radio-tagged paddlefish usually remained in a secondary channel that had low current velocity during all seasons, whereas main channel, main channel border, tailwater, and backwater habitats were seldom used. Paddlefish strongly selected areas that were deep; about 62% of paddlefish locations were in areas with more than 6 m of depth, although this habitat constituted only 14.5% of the total study area. However, paddlefish used significantly shallower areas during the night than during the day. Paddlefish moved significantly larger distances at night than during the day in spring and fall, but differences in movement among diel periods during summer were not significant. Our research suggests that radiotelemetry studies that need to determine depth use or movement of paddlefish during small time scales may need to incorporate a diel component. However, study objectives to determine use of general habitat types by radio-marked paddlefish can be adequately met by tracking during the day.

Women with early breast cancer were offered the choice of a mastectom lurnpectomy plus radiotherapy, or entry in a trial in which the alrdcation to either type of treatment was randomized. Few women chose the trial, and most were relieved that a choice was available. Othel patients, for whom it was decided that a mastectomy was the only viable treatment on medical grounds, were offered breast reconstruction whenever it was technically feasible. Psychosocial adaptation was measured using tests of anxiety, depression, marital adjustment, body satisfaction, self-esteem, sociability, and life change. Tests were given before surgery at intervals up to one year afterward. The degree of concern the women felt about the disease, their appearance, and the treatment was also assessed. The major difference among the groups was in the degree of concern about appearance. Women who rated high in this regard (the younger patients) tended to choose conservative surgery or reconstruction when a mastectomy was necessary. Generally, the adjustment to treatment was good in all the groups, despite some anxiety when the patients were in the hospital for surgery. Tailoring the treatment to each woman's preference resulted in low psychological morbidity.

Purpose. The effect of elevated serum alpha-1 -acid glycoprotein (AAG) concentrations on the steady-state serum and brain levels of imipramine and its metabolite desipramine was assessed. This was approached using a novel strain of transgenic mice whose basal endogenous serum AAG levels were 8.6-fold elevated over normal.

Five methods for forming empirical frequency distributions are outlined. A specific implementation of each is described, and theoretical comparison of their speed and storage is supplemented by simulation data to give a series of recommendations about the appropriateness of each for different situations. The index method is the fastest of those considered, but often uses excessive space. A method based on height-balanced trees is economical of space, and still has good speed. A method based on Quicksort is faster than the tree method, but uses more space.

I compared quantitative samples collected by a drop net, a pop net and an electrofishing frame from vegetated habitats of a backwater lake in the upper Mississippi River. All gears sampled an area of 5.6 m2. Catches with all three gears were dominated by juvenile centrarchids, mainly bluegills Lepomis macrochirus. In vegetated, turbid water, catches were significantly less with the electrofishing frame than with the two nets because observing and netting stunned fish was difficult. Capture efficiencies with the electrofishing frame were much higher in nonvegetated, relatively clear water (mean efficiency, 80%) than in vegetated, turbid water (mean efficiency, 5%). Catches with the drop net and pop net were similar in both number and species composition. Both the pop net and drop net were well suited for collecting quantitative samples of small fish from vegetation.

Reactions of (η5-C5H5)Re(NO)(PPh3)(OTf) (1) with pyridine, quinoline, and isoquinoline give the respective σ-adducts [(η5-C5H5)Re(NO)(PPh3)(NCxHy)]+TfO- (2-4) in 86-95% yields. However, 1 and 8-methylquinoline do not react in refluxing xylene (16 h). Reactions of (+)-(R)-1 with quinoline and isoquinoline give (–)-(S)-3 and (+)-(S)-4. Both products form with retention of configuration at rhenium and in >98% ee, as assayed by subsequent reactions with (CH3CH2)4N+CN- to give (+)-(S)-(η5-C5H5)Re(NO)(PPh3)(CN). The crystal structures of 3 (triclinic, P1̄, a = 9.879(1) A, b = 16.677(2) A, c = 9.962(1) Å, α = 91.477(3)°, β = 99.155(3)°, γ = 100.633(3)°, Ζ = 2) and 4 (triclinic, P1̄, a = 10.961(2) Å, b = 15.770(2) Å, c = 10.159(1) A, a = 87.65(2)°, β = 109.88(2)°, γ = 101.27(2)°, Z = 2) are determined, and the Re—N conformations analyzed.

Summary Previous reports indicate that in laboratory strains of mice, males are distinct from females in possession of repetitive DNA, notably devoid of Eco RI and Hae III sites and rich in the simple tetranucleotides GATA/GACA. We report here that such sequences originated in an ancestor common to laboratory mice,Mus hortulanus, M. spretus, and possibly alsoM. cookii. Interestingly, other male-specific satellite sequences were detected inM. caroli, M. cookii, M. saxicola, andM. minutoides. This novel satellite is also likely to be composed of simple repetitious sequences, but does not contain GATA and GACA. Thus, the Y chromosome appears to contain a disproportionately large amount of simple repetitious DNA. An attractive explanation for these results is that long tandem arrays of simple repeated sequences are generated at high frequency throughout the genome and that they are retained for a longer time on the Y chromosome due to the absence of homologous pairing at meiosis.

Two groups of patients suffering from persecutory delusions, one consisting of patients also suffering from depression and a non‐depressed group, together with clinically depressed and normal controls matched with the deluded patients for age and intelligence, were asked to rate the frequency with which selected positive, negative and neutral events had happened to themselves and to an average other person in the past, and the frequency with which these events were likely to happen to themselves and to an average other person in the future. Results were similar for both past and expected future events. Non‐depressed‐deluded, depressed‐deluded and depressed patients rated negative events as occurring relatively more frequently in comparison to the normal controls. Depressed participants rated positive events as occurring more frequently to others, whereas the normal participants rated negative events as occurring more often to others. Correlational analyses indicated that depression scores were associated with low estimates of the frequency with which positive events happen to self and high estimates of the frequency with which negative events happen to self. Magical ideation scores, an index of psychosis, were associated with high estimates of the frequency of negative events for both self and others. These findings are interpreted in the context of previous evidence on cognitive biases in deluded patients.

This paper describes the development of a simple paper-and-pencil test designed to measure satisfaction/dissatisfaction with 16 body parts. It is based on the body-cathexis scale of Secord and Jourard (1953) but takes only 2-3 minutes to complete. The factorial structure of the scale is described together with the three summative scales ("general," "head parts" and "body parts" dissatisfaction) which are derived. The internal consistency of the scales was found to be acceptable. Significant positive correlations are also reported with the Body Shape Questionnaire (Cooper et al., 1987). The paper reports data for female comparison groups (college students, nursing students and female volunteers) and for samples of eating disorder patients and overweight subjects. The latter two groups report significantly higher body dissatisfaction than the comparison groups. Finally, it is argued that the scale is useful for work in health related fields and some current applications are briefly described.

Although the assessment of the social, emotional and personality sequelae of traumatic injury is of central clinical and medico-legal importance, no satisfactory standard assessment device for this purpose has yet been developed. A multicentred study of a mixed group of head and spinally injured patients is reported. Factor analysis of a modified version of the relatives' form of the Katz Social Adjustment Scale (KAS - R) yielded 30 first-order factors under three main domains of emotional/psychosocial, physical/intellectual and psychiatric changes, together with seven second-order factors which were readily identifiable in terms of syndromes accompanying traumatic injury. Discriminant function analyses indicated that prediction of patient group using KAS-R data was most accurate using the current study's first-order factors as compared with the original factor structure proposed by Katz and Lyerly or the second-order factors from the current analyses. The modified KAS - R shows considerable promise as an instrument for measuring the complex social, emotional and personality changes following traumatic injury, with special significance for assessing brain-injury victims. The representativeness of the current patient sample and implications for future development of the method are discussed.

Mutagenized stem cells of a cultured mouse teratocarcinoma cell line were selected for resistance to the purine base analog 6-thioguanine. Cells of a resistant clone were completely deficient in activity of the enzyme hypoxanthine phosphoribosyltransferase (HPRT, IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8), the same X-linked lesion as occurs in human Lesch-Nyhan disease. After microinjection into blastocysts of another genetic strain, the previously malignant cells successfully participated in normal embryogenesis and tumor-free, viable mosaic mice were obtained. Cells of tumor lineage were identified by strain markers in virtually all tissues of some individuals. Mature function of those cells was evident from their tissue-specific products (e.g., melanins, liver proteins). These mutagenized teratocarcinoma cells are therefore developmentally totipotent. Retention of the severe HPRT deficiency in the differentiated state was documented in extracts of mosaic tissues by depressed specific activity of the enzyme, and also by presence of unlabeled clones in autoradiographs of explanted cells incubated in [3H]hypoxanthine. Some mosaic individuals had mutant-strain cells in only one or a few tissues. Such animals may provide unique opportunities to identify the tissue sources of particular aspects of the complex disease syndrome. The tissue distribution of HPRT-deficient cells suggests that selection against them is particularly strong in blood of the mosaic mice, as is already known to be the case in human heterozygotes. This phenotypic parallelism supports the expectation that afflicted F1male mice that might be obtained from mutant germ cells can serve as a model of the human disease.

The immediate purpose of the experiment was to establish a means of introducing specific mitochondrially encoded mutant genes into mice. Mouse teratocarcinoma stem cells were used as vehicles for the cytoplasmic markers because of their known capacity for normal somatic and germinal differentiation after injection into blastocysts. The mutation of choice, chloramphenicol resistance (CAPR), was first produced in a melanoma cell line by mutagenesis and selection. The CAPRtrait was then transferred from a resistant melanoma cell to a sensitive (CAPS) teratocarcinoma cell by fusing to the latter only the cytoplasmic portion of the CAPRdonor. This indirect route demonstrated the cytoplasmic provenance of the mutation. Protein synthesis in mitochondria isolated from the cybrid, or cytoplasmic hybrid, cells was barely affected by chloramphenicol, in contrast to the inhibitory influence of the drug on mitochondria of the parent teratocarcinoma line. Cells of the cybrid clone resembled teratocarcinoma cells and retained their ability to form diverse tissues in solid tumors produced from subcutaneous grafts. Cells from the tumors were retransplanted and were tested periodically by culture in chloramphenicol; they were found to be stably CAPReven after 16 weeks in vivoin the absence of the selective agent. The CAPRcybrids were microinjected into blastocysts of another inbred strain and, after transfer to foster mothers, mosaic mice were obtained. They comprised both cybrid- and blastocyst-derived cells in various tissues, as indicated by strain-specific nuclear markers. These results demonstrate successful normal differentiation of the CAPRlineage in vivo. Teratocarcinoma cybrids thus offer a practical portal of entry of preselected mitochondrial genes into mice. This will ultimately permit in vivoinvestigation of maternally transmitted traits, of mitochondrial genetic influences in specialized cells, and of possible roles of cytoplasmic genes in clinical and disease states.

Teratocarcinoma (TCC) stem cells provide unique prospects for the introduction of specific genes into mice, by virtue of their dual capacity for propagation in vitroand for normal differentiation in embryos. In this study, we have demonstrated that foreign genes amenable to selection in culture can be transferred into the stem cells and expressed. These cells maintain expression of the gene for long periods during differentiation in tumors in vivoin the absence of selective pressure. The cells also integrate an unlinked nonselectable gene at high frequency.Addition of the cloned herpes simplex virus (HSV) thymidine kinase (tk; ATP:thymidine 5′-phosphotransferase, EC 2.7.1.21) gene to cultures of tk-TCC cells yielded tk+colonies at a frequency of one colony per 4 μg of plasmid DNA. This transformation efficiency, although appreciably lower than for mouse L tk-cells, permits the isolation of many transformants. The HSV provenance of the transformed phenotype was verified by the characteristic electrophoretic mobility of the tk protein and by neutralization of the tk activity with specific antiserum. Moreover, blot hybridization tests revealed at least one intact copy of the viral tk gene integrated into the DNA of transformed cells. When injected into syngeneic mice, the cells formed solid tumors with various differentiating tissues. From blot hybridization comparisons with their cell lines of origin, seven of nine tumors examined had maintained the HSV tk gene without significant loss or rearrangement. Viral tk enzyme activity could also be demonstrated in at least some of the tumors. Cotransfer of the cloned human β-globin gene along with the unlinked HSV tk gene was successful in 2 of 10 tk+transformants. Thus, defined genes can be stably introduced into TCC cells in culture and maintained in vivoin a form in which they are transcribed and translated to produce a functional protein.

-The cumulative effects of collection, handling, and marking with fluorescent pigment on the mortality of adult minnows, young-of-the-year centrarchids, and large centrarchids and percids was determined at five water temperatures (10-20.6°C) in field trials. There have been few field trials of this type. The mortality of centrarchids and percids was directly related to temperature and decreased noticeably when the temperature was below 19.5°C. The mortality of minnows decreased somewhat as river temperatures cooled but was always at least 50%. Variation was high in the temperature-related patterns of mortality in different taxa and sizes of fish. This variation complicates the accuracy and usefulness of pigment in marking field-collected fish for mark-recapture studies in warmwater systems.

Two models of pop nets were developed to sample fish in shallow riverine waters, one for use in vegetated areas and the other for nonvegetated areas. Both nets have a mechanical release mechanism that can be tripped from the water surface. Replicated field tests were conducted to compare pop-net catches with bag-seine collections every 2 weeks from May through mid-October. Overall, total catch per effort did not vary significantly (P< 0.05) between the two gears at either the vegetated or nonvegetated site. However, collections with the pop net were not as diverse as with the seine at either sampling site, perhaps because the area sampled by pop nets (5.6 m2) was smaller than the area swept by the average seine haul (70-140 m2). The pop net effectively sampled fish in shallow nonvegetated habitats and was useful in heavily vegetated areas where seining or electroshocking was difficult.