Movers and stayers: how residential selection contributes to the association between female body mass index and neighborhood characteristics.

BACKGROUND/OBJECTIVES: To examine how a woman's current body mass index (BMI) is associated with nonrandom residential migration that is based on the average BMI of her origin and destination neighborhoods. SUBJECTS/METHODS: Among women having at least two children, all birth certificates from Salt Lake county from 1989 to 2010 (n=34 010) were used to obtain prepregnancy weights before the first and second births, residential location and sociodemographic information. Census data were used for measures of walkability of neighborhoods. RESULTS: After adjustments for age, education, race/ethnicity and marital status, obese women living in the leanest neighborhoods are found to be three times more likely (odds ratio (OR)=3.03, 95% confidence interval (CI) 2.06-4.47) to move to the heaviest neighborhoods relative to women with healthy weight (BMI between 18 and 25 kg m(-2)). Conversely, obese women in the heaviest neighborhoods are 60% less likely (OR=0.39, 95% CI 0.22-0.69) to move to the leanest neighborhoods relative to healthy weight women. Indicators of relatively greater walkability (older housing, greater proportion of residents who walk to work) and higher median family income characterize leaner neighborhoods. CONCLUSIONS: The findings are consistent with the hypothesis that nonrandom selection into and out of neighborhoods accounts for some of the association between BMI and neighborhood characteristics.

Maternal and neonatal outcomes for pregnancies before and after gastric bypass surgery.

BACKGROUND: Interaction between maternal obesity, intrauterine environment and adverse clinical outcomes of newborns has been described. METHODS: Using statewide birth certificate data, this retrospective, matched-control cohort study compared paired birth weights and complications of infants born to women before and after Roux-en-Y gastric bypass surgery (RYGB) and to matched obese non-operated women in several different groups. Women who had given birth to a child before and after RYGB (group 1; n=295 matches) and women with pregnancies after RYGB (group 2; n=764 matches) were matched to non-operated women based on age, body mass index (BMI) prior to both pregnancy and RYGB, mother's race, year of mother/s birth, date of infant births and birth order. In addition, birth weights of 13 143 live births before and/or after RYGB of their mothers (n=5819) were compared (group 3). RESULTS: Odds ratios (ORs) for having a large-for-gestational-age (LGA) neonate were significantly less after RYGB than for non-surgical mothers: ORs for groups 1 and 2 were 0.19 (0.08-0.38) and 0.33 (0.21-0.51), respectively. In contrast, ORs in all three groups for risk of having a small for gestational age (SGA) neonate were greater for RYGB mothers compared to non-surgical mothers (ORs were 2.16 (1.00-5.04); 2.16 (1.43-3.32); and 2.25 (1.89-2.69), respectively). Neonatal complications were not different for group 1 RYGB and non-surgical women for the first pregnancy following RYGB. Pregnancy-induced hypertension and gestational diabetes were significantly lower for the first pregnancy of mothers following RYGB compared to matched pregnancies of non-surgical mothers. CONCLUSION: Women who had undergone RYGB not only had lower risk for having an LGA neonate compared to BMI-matched mothers, but also had significantly higher risk for delivering an SGA neonate following RYGB. RYGB women were less likely than non-operated women to have pregnancy-related hypertension and diabetes.

Roux-en-Y gastric bypass in rats increases sucrose taste-related motivated behavior independent of pharmacological GLP-1-receptor modulation.

Roux-en-Y gastric bypass (RYGB) surgery has been shown to decrease consummatory responsiveness of rats to high sucrose concentrations, and genetic deletion of glucagon-like peptide-1 receptors (GLP-1R) has been shown to decrease consummatory responsiveness of mice to low-sucrose concentrations. Here we assessed the effects of RYGB and pharmacological GLP-1R modulation on sucrose licking by chow-fed rats in a brief-access test that assessed consummatory and appetitive behaviors. Rats were tested while fasted presurgically and postsurgically and while nondeprived postsurgically and 5 h after intraperitoneal injections with the GLP-1R antagonist exendin-3(9-39) (30 µg/kg), agonist exendin-4 (1 µg/kg), and vehicle in 30-min sessions during which a sucrose concentration series (0.01-1.0 M) was presented in 10-s trials. Other rats were tested postsurgically or 15 min after peptide or vehicle injection while fasted and while nondeprived. Independent of food-deprivation state, sucrose experience, or GLP-1R modulation, RYGB rats took 1.5-3× as many trials as sham-operated rats, indicating increased appetitive behavior. Under nondeprived conditions, RYGB rats with presurgical sucrose experience licked more to sucrose relative to water compared with sham-operated rats. Exendin-4 and exendin-3(9-39) impacted 0.3 M sucrose intake in a one-bottle test, but never interacted with surgical group to affect brief-access responding. Unlike prior reports in both clearly obese and relatively leaner rats given RYGB and in GLP-1R knockout mice, we found that neither RYGB nor GLP-1R blockade decreased consummatory responsiveness to sucrose in our less obese chow-fed rats. Collectively, these results highlight the fact that changes in taste-driven motivated behavior to sucrose after RYGB and/or GLP-1R modulation are very model and measure dependent.

Awareness in children: a secondary analysis of five cohort studies.

Five recent cohort studies have shown a frequency of awareness in paediatric anaesthesia of between 0.2% and 1.2%, but they were not individually large enough to identify risk factors. This study pooled raw data from these five studies to identify factors associated with awareness in children. The outcome of awareness was taken as the cases judged to be most likely awareness cases in each study. Logistic regression was used to identify awareness-associated factors. A combined sample of 4486 anaesthetics revealed 33 cases of awareness. Unadjusted analysis demonstrated weak evidence that nitrous oxide used as an anaesthetic maintenance adjunct was associated with awareness (OR 2.04 (95% CI 0.97-4.33), p=0.06), and some evidence that use of a tracheal tube was associated with awareness (OR 2.78 (95% CI 1.11-6.94), p=0.03). Multivariable regression analysis revealed that nitrous oxide maintenance and use of a tracheal tube were independently associated with awareness (nitrous oxide, OR 2.4 (95% CI 1.08-5.32), p=0.03; tracheal tube, OR 3.0 (95% CI 1.20-7.56), p=0.02).

Correct folding of alpha-lytic protease is required for its extracellular secretion from Escherichia coli.

alpha-Lytic protease is a bacterial serine protease of the trypsin family that is synthesized as a 39-kD preproenzyme (Silen, J. L., C. N. McGrath, K. R. Smith, and D. A. Agard. 1988. Gene (Amst.). 69: 237-244). The 198-amino acid mature protease is secreted into the culture medium by the native host, Lysobacter enzymogenes (Whitaker, D. R. 1970. Methods Enzymol. 19:599-613). Expression experiments in Escherichia coli revealed that the 166-amino acid pro region is transiently required either in cis (Silen, J. L., D. Frank, A. Fujishige, R. Bone, and D. A. Agard. 1989. J. Bacteriol. 171:1320-1325) or in trans (Silen, J. L., and D. A. Agard. 1989. Nature (Lond.). 341:462-464) for the proper folding and extracellular accumulation of the enzyme. The maturation process is temperature sensitive in E. coli; unprocessed precursor accumulates in the cells at temperatures above 30 degrees C (Silen, J. L., D. Frank, A. Fujishige, R. Bone, and D. A. Agard. 1989. J. Bacteriol. 171:1320-1325). Here we show that full-length precursor produced at nonpermissive temperatures is tightly associated with the E. coli outer membrane. The active site mutant Ser 195----Ala (SA195), which is incapable of self-processing, also accumulates as a precursor in the outer membrane, even when expressed at permissive temperatures. When the protease domain is expressed in the absence of the pro region, the misfolded, inactive protease also cofractionates with the outer membrane. However, when the folding requirement for either wild-type or mutant protease domains is provided by expressing the pro region in trans, both are efficiently secreted into the extracellular medium. Attempts to separate folding and secretion functions by extensive deletion mutagenesis within the pro region were unsuccessful. Taken together, these results suggest that only properly folded and processed forms of alpha-lytic protease are efficiently transported to the medium.

Military uses of uranium: keeping the u.s. Energy accounts.

Present accounts of U.S. energy consumption are incomplete in two ways: they include neither the direct military uses of nuclear energy nor the mostly military, nonfuel uses of uranium. Preliminary estimates indicate that significant distortions are created in the data on U.S. nuclear energy consumption patterns as a result of these omissions.

Relative potencies of bupivacaine, levobupivacaine, and ropivacaine for neonatal spinal anaesthesia.

BACKGROUND: Comparing the relative potency of new local anaesthetics such as levobupivacaine and ropivacaine with bupivacaine by the minimum local analgesic concentration model has not been described for neonatal spinal anaesthesia. This information is important to compare agents and to determine the most effective spinal dose. METHODS: We performed a two-stage study to determine the ED50, the ED95, and the relative analgesic potency of isobaric spinal bupivacaine, levobupivacaine, and ropivacaine in infants. In phase 1, 81 infants were randomized in a Dixon-Massey study to describe the minimum local analgesic dose. In phase 2, a further 70 patients were randomly allocated to receive spinal anaesthesia with doses in the upper dose-response range to define the ED95. RESULTS: The ED50 doses for bupivacaine, levobupivacaine, and ropivacaine were estimated by isotonic regression to be 0.30 mg kg(-1) [95% confidence interval (CI) 0.25-0.43], 0.55 mg kg(-1) (0.50-0.64), and 0.50 mg kg(-1) (0.43-0.64), respectively. The ED(95), respectively, of bupivacaine, levobupivacaine, and ropivacaine were 0.96 mg kg(-1) (95% CI 0.83-0.98), 1.18 mg kg(-1) (1.05-1.22), and 0.99 mg kg(-1) (0.73-1.50). The relative potency ratios at the ED(50) were bupivacaine:levobupivacaine 0.55 (95% CI 0.39-0.88), bupivacaine:ropivacaine 0.61 (0.41-1.00), and levobupivacaine:ropivacaine 1.09 (0.84-1.45). CONCLUSIONS: Appropriate doses for infant spinal anaesthesia are 1 mg kg(-1) of isobaric 0.5% bupivacaine and ropivacaine and 1.2 mg kg(-1) of isobaric 0.5% levobupivacaine.

Machine-learned modeling of PM2.5 exposures in rural Lao PDR.

This study presents a machine-learning-enhanced method of modeling PM2.5 personal exposures in a data-scarce, rural, solid fuel use context. Data collected during a cookstove (Africa Clean Energy (ACE)-1 solar-battery-powered stove) intervention program in rural Lao PDR are presented and leveraged to explore advanced techniques for predicting personal exposures to particulate matter with aerodynamic diameter smaller than 2.5 µm (PM2.5). Mean 48-h PM2.5 exposure concentrations for female cooks were measured for the pre- and post-intervention periods (the "Before" and "After" periods, respectively) as 123 µg/m3 and 81 µg/m3. Mean 48-h PM2.5 kitchen air pollution ("KAP") concentrations were measured at 462 µg/m3 Before and 124 µg/m3 After. Application of machine learning and ensemble modeling demonstrated cross-validated personal exposure predictions that were modest at the individual level but reasonably strong at the group level, with the best models producing an observed vs. predicted r2 between 0.26 and 0.31 (r2 = 0.49 when using a smaller, un-imputed dataset) and mean Before estimates of 119-120 µg/m3 and After estimates of 86-88 µg/m3. This offered improvement over one typical method of predicting exposure - using a kitchen exposure factor (the ratio of exposure to KAP)- which demonstrated an r2 ~ 0.03 and poorly estimated group average values. The results of these analyses highlight areas of methodological improvement for future exposure assessments of household air pollution and provide evidence for researchers to explore the advantages of further incorporating machine learning methods into similar research across wider geographic and cultural contexts.

Simultaneous downregulation of CDK inhibitors p18(Ink4c) and p27(Kip1) is required for MEN2A-RET-mediated mitogenesis.

Multiple endocrine neoplasia type 2A (MEN2A) is predisposed by mutations in the RET proto-oncogene. Low expression of the cyclin-dependent kinase inhibitor (CDKI) p27(Kip1) is present in thyroid tumors, and recent evidence demonstrates p27 downregulation by the active RET mutant, RET/PTC1, found in papillary thyroid carcinoma. This implicates decreased p27 activity as an important event during thyroid tumorigenesis. However, p27(-/-) mice develop MEN-like tumors only in combination with loss of another CDKI, p18(Ink4c). This suggests that p18 and p27 functionally collaborate in suppression of tumorigenesis, that loss of both is critical in the development of MEN tumors and that both p18 and p27 are regulated by RET. We report that induction of the constitutively active MEN2A-specific RET mutant, RET2A(C634R), correlates with reduced p18/p27, and elevated cyclin D protein levels, leading to increased CDK activity, increased pRb phosphorylation and proliferation under growth arrest conditions. Mechanistically, RET2A represses p18/p27 mRNA levels while elevating cyclin D1 mRNA levels. RET2A expression also correlates with decreased p27 protein stability. RET2A-mediated regulation of p18 and p27, but not of cyclins D1 and D2, requires functional mitogen-activated protein kinase signaling. Additionally, RET2A-dependent p18 repression is required and sufficient to increase cell proliferation. Perhaps most significantly, MEN2A adrenal tumors also display these changes in cell cycle expression profile, demonstrating the biological relevance of our cell culture studies. Our results demonstrate for the first time that RET2A regulates p18, and suggest that loss of not only p27 but also of p18 expression is a key step in MEN tumorigenesis.

I.V. acetaminophen pharmacokinetics in neonates after multiple doses.

BACKGROUND: Pharmacokinetics of an i.v. prodrug of acetaminophen (propacetamol) in neonates after repeat dosing are reported, with scant data for i.v. acetaminophen formulation. METHODS: Neonates from an intensive care unit received 6-hourly prn i.v. acetaminophen dosed according to postmenstrual age (PMA): 28-32 weeks, 10 mg kg(-1); 32-36 weeks, 12.5 mg kg(-1); and > or =36 weeks, 15 mg kg(-1). A maximum of five blood samples for assay and liver function tests (LFTs) were collected. A one-compartment linear disposition model (zero-order input; first-order elimination) was used to describe time-concentration profiles using population modelling (NONMEM). RESULTS: Fifty neonates, median (range) PMA 38.6 (32-45) weeks, mean (SD) weight 2.9 (0.7) kg, received a mean of 15 doses over a median 4 days with 189 serum acetaminophen and 231 LFT measurements. Standardized population parameter estimates for a term neonate were clearance (CL) 5.24 (CV 30.5%) litre h(-1) 70 kg(-1) and volume of distribution (V) 76 (29.6%) litre 70 kg(-1). CL increased with PMA from 4.4 litre h(-1) 70 kg(-1) at 34 weeks to 6.3 litre h(-1) 70 kg(-1) at 46 weeks. The presence of unconjugated hyperbilirubinaemia was associated with reduced CL: 150 micromol litre(-1) associated with 40% CL reduction. Acetaminophen concentrations between 10 and 23 mg litre(-1) at steady state are predicted after 15 mg kg(-1) 6-hourly for a neonate of PMA 40 weeks. Hepatic enzyme analysis of daily samples changed significantly for one patient whose alanine aminotransferase concentration tripled. CONCLUSIONS: The parameter estimates are similar to those described for propacetamol. There was no evidence of hepatotoxicity. Unconjugated hyperbilirubinaemia impacts upon CL, dictating dose reduction.

Lung function and symptoms among indigenous Mayan women exposed to high levels of indoor air pollution.

SETTING: Indoor air pollution from burning of biomass fuel in open fires is a known risk factor for chronic obstructive pulmonary disease (COPD) in developing countries. OBJECTIVE: To estimate the prevalence of respiratory symptoms and lung function among women in rural Guatemala and to describe the methods and practical issues associated with the assessment of respiratory health. DESIGN: Information about respiratory symptoms, lung function and individual measurement of exposure was collected cross-sectionally among 350 Mayan-Indian women aged 15-50 years who used traditional open fires. RESULTS: These women, exposed to indoor air pollution since birth, had a relatively high prevalence of cough (22.6%), phlegm (15.1%), wheeze (25.1%) and tightness in the chest (31.4%). Respiratory symptoms were positively associated with exposure levels. Lung function was higher than the most feasible reference population (average above predicted forced expiratory volume in 1 s [FEV(1)] +4.5% and forced vital capacity [FVC] +4.2%). Only one woman had a FEV(1)/FVC ratio lower than 70%. CONCLUSIONS: According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, almost one third of these young non-smoking women were at risk (stage 0) of developing COPD. The methodological issues encountered during the study highlight the importance of standardising approaches to local adaptation of established questionnaires to study respiratory health in rural areas of developing countries.

China at the crossroads: the economics of tobacco and health.

OBJECTIVE: To analyse economic aspects of tobacco control policy issues in China. METHODS: Published and collected survey data were used to analyse economic consequences of smoking. Economic analysis was used to address the role of tobacco farmers and the cigarette industry in the Chinese economy. RESULTS: In the agricultural sector, tobacco has the lowest economic rate of return of all cash crops. At the same time, the tobacco industry's tax contribution to the central government has been declining. CONCLUSION: Economic gains become less important as the negative health impact of smoking on the population garners more awareness. China stands at a crossroads to implement the economic promises of the World Health Organization's Framework Convention on Tobacco Control and promote the health of its population.

Breast cancer mortality among immigrants in Australia and Canada.

BACKGROUND: By moving between geographic regions with differing levels of breast cancer risk, migrant populations of women provide a unique opportunity to examine the impact of exposure to new environments and lifestyles on breast cancer risk. Breast cancer incidence and mortality rates for the majority of migrant groups originating from countries with low breast cancer risk have been found to increase toward the rates observed in destination countries with populations at higher risk for this disease. Because very little information exists on migrants from high- to low-risk countries, it is not known whether rates for these groups decrease or whether migrant groups generally experience increases in breast cancer rates. PURPOSE: To address these questions, we determined the breast cancer mortality rates for women from both lower and higher risk countries who had immigrated to Australia and Canada and compared these rates with those exhibited by the population in the origin country and by the destination native-born population. METHODS: Individual mortality records covering the years 1984 through 1988 and 1986 census data for Australia and Canada were obtained. Direct age-standardized mortality rates and rate ratios (and their 95% confidence intervals) were calculated for immigrant groups in Australia and Canada. Age-standardized rate ratios by length of residence in Australia were calculated. Weighted regression analyses of observed and expected mortality changes were performed. RESULTS: In Australia, the mortality rates for 12 (75%) of 16 immigrant groups from lower risk countries and 10 (71.4%) of 14 groups from higher risk countries shifted toward the rate of native-born Australians. In Canada, the rates for 12 (60%) of 20 immigrant groups from lower risk countries and four (80%) of five groups from higher risk countries converged to the rate of native-born Canadians. Overall, the extent of convergence (shift of immigrant's mortality rate in origin country toward rate of native-born population) was 50% for immigrants in Australia and 38% for immigrants in Canada. Although there was not a consistent pattern of convergence with length of residence in Australia, after 30 or more years, the mortality rates of 15 (83.3%) of 18 immigrant groups had shifted toward the rate of the native-born Australians. Because of the small number of deaths in many of the immigrant groups studied, the observed differences in the breast cancer mortality age-standardized rates between the origin country and immigrant group, although often substantial, were seldom statistically significant. CONCLUSIONS: Breast cancer mortality rates among women in the majority of immigrant groups shifted from the rate observed in their country of origin toward the rate of the native-born population in the destination country. IMPLICATIONS: These findings indicate that environmental and lifestyle factors associated with the new place of residence influence the breast cancer rates of immigrants and also suggest that, since most migrants migrate as adults, the risk of breast cancer can be altered in later life.

Energy intake: its relationship to colon cancer risk.

A case-control study was conducted to assess the role of diet in the etiology of colon cancer. Diet was measured by means of a comprehensive quantifiable food frequency history instrument in 246 cases and 484 controls drawn from the general population of Utah. Each subject's diet was described by major nutrient groups and total energy based on the nutritional content of foods reported. Cases reported higher daily food intake 5 years preceding diagnosis than controls [men, rate ratio (RR) = 2.5; women, RR = 3.6], as measured by total energy content of the diet. Higher risk of colon cancer with increasing energy intake was independent of stage of disease at diagnosis and obesity, as measured by body mass. Fat, protein, and carbohydrate intake all had elevated RRs but could not be assessed as risk factors independent of energy intake because of their strong correlations with total calories. Due to the higher energy intake of the cases, odds ratios for the daily intake of dietary fiber and vitamins A and C were also greater than 1. However, adjusting for caloric intake removed this effect, and dietary fiber showed a weak protective effect. Total energy intake must be evaluated before attempting to assign a causal role to any food or nutrient that may be postulated to play a role in colon cancer.

The vital role of science in global policy decision-making: An analysis of past, current, and forecasted trends and issues in global red meat trade and policy.

As global populations and economies change, the dynamics of global trade and policy change as well. In analyzing the past trends and projections for global populations, economic developments, animal product production and consumption, global trade policy, and current issues being faced, one can begin to make some predictions or projections as to how the global red meat and poultry infrastructure will change and, more importantly, point to areas where a proactive approach is necessary to shape these changes to meet the most globally beneficial end. Many issues face the global red meat industry, from food safety to animal disease, and are becoming more and more complicated as consumer knowledge increases and as politics intervene. Internationalized science is key and vital in the future of global trade policy as science can address the more informed consumer in a manner, which reduces anxiety over unknowns. The role of the industry is to provide the information and knowledge to the consumer necessary to convey the validity of globally accepted standards, which relate to ensuring consumer safety, animal welfare, and provide assurances that these standards are being met within the production sector.

Familial colorectal cancer risk by subsite of primary cancer: a population-based study in Utah.

BACKGROUND: Familial occurrence is common in colorectal cancer (CRC), but whether this increased familial risk differs by colonic subsite of the index patients CRC is not well understood. AIM: To quantify the risk of CRC in first-degree (FDR), second-degree (SDR) and first cousin (FC) relatives of individuals with CRC, stratified by subsite in the colorectum and age at diagnosis. METHODS: Colorectal cancers diagnosed between 1980 and 2010 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age and gender-matched CRC-free controls were selected to form the comparison group for determining CRC risk in relatives using Cox regression analysis. RESULTS: Of the 18,208 index patients diagnosed with CRC, 6584 (36.2%) were located in the proximal colon, 5986 (32.9%) in the distal colon and 5638 (31%) in the rectum. The elevated risk of CRC in relatives was similar in analysis stratified for CRC colorectal subsites in the index cases. FDR had similarly elevated risk of all site CRC, whether the index patient had cancer in the proximal colon [hazards ratio (HR): 1.85; 95% CI: 1.70-2.02], distal colon (HR: 1.90; 95% CI: 1.73-2.08) or rectum (HR: 1.83; 95% CI: 1.66-2.02) compared to relatives of controls. This risk was consistently greater for FDR when cases developed CRC below the age of 60 years. CONCLUSIONS: Relatives of CRC patients have a similarly elevated risk of CRC regardless of colonic tumour subsite in the index patient, and it is greatest for relatives of younger age index cases.

The Haarscheibe.

The Haarscheibe is a specialized spot of epidermis containing many Merkel cell-neurite complexes. It is a highly sensitive, slowly adapting, modality-specific touch receptor occurring in all mammals. Its exact role in signaling sensation in human beings is undetermined, and the function of Merkel cells, with their distinctive cytoplasmic granules, in transducing mechanical force into neural action potentials remains to be determined.

Molecular analysis of the gene encoding alpha-lytic protease: evidence for a preproenzyme.

A 1.7-kb EcoRI fragment containing the structural gene for alpha-lytic protease has been cloned from Lysobacter enzymogenes 495 chromosomal DNA: the first example of a gene cloned from this organism. The protein sequence deduced from the nucleotide sequence encoding this serine protease matches the published amino acid sequence [Olson et al., Nature 228 (1970) 438-442] precisely. Sequence analysis and S1 mapping indicate that, like subtilisin [e.g., Wells et al., Nucleic Acids Res. 11 (1983) 7911-7925] alpha-lytic protease is synthesized as a pre-pro protein (41 kDa) that is subsequently processed to its mature extracellular form (20 kDa). This first finding of a large N-terminal protease precursor in a Gram-negative bacterial protease strengthens the hypothesis that large precursors may be a general property of extracellular bacterial proteases, and suggests that the N- or C-terminal location of the precursor segment may be significant.

Genetic variation in the spread of Drosophila subobscura from a nonequilibrium population.

Drosophila subobscura was first identified in North America in the early 1980s, and a newer D. subobscura population in Utah appears to have been established more than 10 years later. In this study, we use nuclear microsatellite allele frequencies, mitochondrial restriction fragment length polymorphism (RFLP) allele frequencies, and computer simulations to investigate possible scenarios of how this species has spread across North America. Our method develops a 95% confidence interval for the maximum and minimum number of founders that could have colonized the new population given various scenarios for spread. Unlike many other methods, it may be applied to nonequilibrium source populations given certain conditions. We find that observed allele frequency differences between newer and older D. subobscura populations are consistent with very few inseminated females being transported east from the coast in a single step or with larger numbers of colonizers invading after several intermediate steps. They are not consistent with a large, panmictic population of D. subobscura colonizing Utah in a single step.

The genetics of reproductive isolation and the potential for gene exchange between Drosophila pseudoobscura and D. persimilis via backcross hybrid males.

Hybrid male sterility, hybrid inviability, sexual isolation, and a hybrid male courtship dysfunction reproductively isolate Drosophila pseudoobscura and D. persimilis. Previous studies of the genetic bases of these isolating mechanisms have yielded only limited information about how much and what areas of the genome are susceptible to interspecies introgression. We have examined the genetic basis of these barriers to gene exchange in several thousand backcross hybrid male progeny of these species using 14 codominant molecular genetic markers spanning the five chromosomes of these species, focusing particularly on the autosomes. Hybrid male sterility, hybrid inviability, and the hybrid male courtship dysfunction were all associated with X-autosome interactions involving primarily the inverted regions on the left arm of the X-chromosome and the center of the second chromosome. Sexual isolation from D. pseudoobscura females was primarily associated with the left arm of the X-chromosome, although both the right arm and the center of the second chromosome also contributed to it. Sexual isolation from D. persimilis females was primarily associated with the second chromosome. The absence of isolating mechanisms being associated with many autosomal regions, including some large inverted regions that separate the strains, suggests that these phenotypes may not be caused by genes spread throughout the genome. We suggest that gene flow between these species via hybrid males may be possible at loci spread across much of the autosomes.