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PubMed1987

Longitudinal differentiation of metaphase chromosomes of Indian muntjac as studied by restriction enzyme digestion, in situ hybridization with cloned DNA probes and distamycin A plus DAPI fluorescence staining.

The longitudinal differentiation of metaphase chromosomes of the Indian muntjac was studied by digestion with restriction enzymes, in situ hybridization with cloned DNA probes and distamycin A plus DAPI (4'-6-diamidino-2-phenylindole) fluorescence staining. The centromeric regions of chromosomes 3 and 3 + X of a male Indian muntjac cell line were distinct from each other and different from those of other chromosomes. Digestion with a combination of EcoRI and Sau3A revealed a pattern corresponding to that of C-banding. Digestion with AluI, EcoRII or RsaI yielded a band specific to the centromeric region only in chromosomes 3 and 3 + X. Furthermore, HinfI digestion yielded only a band at the centromeric region of chromosome 3, whereas DA-DAPI staining revealed a single band limited to the extreme end of the C-band heterochromatin of the short arm of 3 + X. These results suggest that centromeres of Indian muntjac chromosomes contain at least four different types of repetitive DNA. Such diversity in heterochromatin was also confirmed by in situ hybridization using specific DNA probes isolated and cloned from highly repetitive DNA families. Heterozygosity between chromosome homologs was revealed by restriction enzyme banding. Evidence is presented for the presence of nucleolus organizer regions (NORs) on the long arm of chromosome 1 as well as on the secondary constrictions of 3 and 3 + X.

Animals↗
PubMed2025

Temporal and geographical lineage dynamics of invasive Streptococcus pyogenes in Australia from 2011 to 2023: a retrospective, multicentre, clinical and genomic epidemiology study.

BACKGROUND: Defining the temporal dynamics of invasive Streptococcus pyogenes (group A Streptococcus) and differences between hyperendemic and lower-incidence regions provides crucial insights into pathogen evolution and, in turn, informs preventive measures. We aimed to examine the clinical and temporal lineage dynamics of S pyogenes across different disease settings in Australia to improve understanding of drivers of pathogen diversity. METHODS: In this retrospective, multicentre, clinical and genomic epidemiology study, we identified cases of invasive S pyogenes infection from normally sterile sites between Jan 1, 2011, and Feb 28, 2023. Data were collected from five hospital networks across low-incidence regions in temperate southeast Australia and the hyperendemic, tropical, and largely remote Top End of the Northern Territory of Australia. The crude incidence rate ratio (IRR) of bloodstream S pyogenes infection comparing the Top End and southeast Australia and in First Nations people compared with non-First Nations people was estimated by quasi-Poisson regression. We estimated odds ratios (ORs) of intensive care unit (ICU) admission, in-hospital mortality, and 30-day mortality for the Top End versus southeast Australia using logistic regression. Retrieved and successfully sequenced isolates were assigned lineages at whole-genome resolution. Temporal trends in the composition of co-circulating lineages were compared between the two regions. We used an S pyogenes-specific multistrain simulated transmission model to examine the relationship between host population-specific parameters and observed pathogen lineage dynamics. The prevalence of accessory genes (those present in 5-95% of all genomes) was compared across geographies and temporal periods to investigate genomic drivers of diversity. FINDINGS: We identified 500 cases of invasive S pyogenes infection in patients in the Top End and 495 cases in patients in southeast Australia. The crude IRR of bloodstream infection for the Top End compared with southeast Australia was 5·97 (95% CI 4·61-7·73) across the entire study period; in the Top End, infection disproportionately affected First Nations people compared with non-First Nations people (5·41, 4·28-6·89). The odds of in-hospital mortality (OR 0·43, 95% CI 0·26-0·70), 30-day mortality (0·38, 0·23-0·63), and ICU admission (0·42, 0·30-0·59) were lower in the Top End than in southeast Australia. Longitudinal lineage analysis of 642 S pyogenes genomes identified waves of replacement with distinct lineages in the Top End, whereas southeast Australia had a small number of dominant lineages that persisted and cycled in frequency. The transmission model qualitatively reproduced a similar pattern of replacement with distinct lineages when using a high transmission rate, small population size, and high levels of human movement-characteristics similar to those of communities in the hyperendemic Top End. Using a lower transmission rate, larger population size, and lower levels of migration similar to those of communities in urbanised southeast Australia, the transmission model qualitatively reproduced a pattern of dominant lineages that cycled in frequency. Despite distinct circulating lineages, the prevalence of accessory genes in the bacterial population was maintained across geographies and temporal periods. INTERPRETATION: In a hyperendemic setting, the replacement of distinct S pyogenes lineages occurred in waves, which could be linked to the disproportionate burden of disease and sparse human population in this setting. The maintenance of bacterial gene frequency could be consistent with multilocus selection. These findings suggest that lineage-specific interventions-such as vaccines under development-should consider disease setting and, without broad cross-protection, might lead to lineage replacement. FUNDING: National Health and Medical Research Council, and Leducq Foundation.

Humans↗
PubMed1997

A Reaction-Diffusion Model can Account for the Anatomical Pattern of the Cardiac Conal Valves in Fish

The conus arteriosus of fish bears a variable number of swallownest-like valves arranged in transverse rows. We propose that a reaction-diffusion mechanism coupled with the specific growth dynamics of the conus arteriosus, and probably, with a system of positional information, can account for the pattern formation of the conal valves in these primitive vertebrates. The reaction-diffusion mechanism, according to our hypothesis, would determine the regular arrangement of the places where the endocardial cells are activated and they transform into mesenchymal cells. These cells populate the subendocardial space, giving rise to the primordia of the conal valves. We have carried out simple computer simulations, based on reaction-diffusion/lateral inhibition models, which were able to generate all the anatomical diversity of the fish conal valves allowing changes only in the growth rate of the structure. Furthermore, we have found similarities between the sequential morphologies generated by our simulations and those actually occurring in embryos of Scyliorhinus canicula. We have derived three testable predictions from our hypothesis: (1) the number of discrete areas of epithelial-mesenchymal transition should correlate with the definitive number of valves in the conus arteriosus; (2) the small valves intercalated between the large ones should develop later than these latter; and (3) the longitudinal growth rate of the conus arteriosus in fish should be proportional to the number of transverse rows of valves. Copyright 1997 Academic Press Limited

Journal Article↗
PubMed2025

Distinct modes of evolution drive HIV escape from two broadly neutralizing antibodies.

Broadly neutralizing antibodies (bNAbs) show promise for HIV treatment and prevention, but are vulnerable to resistance evolution. Comprehensively understanding in vivo viral escape from individual bNAbs is necessary to design bNAb combinations that will provide durable responses. We characterize viral escape from two such bNAbs, 10-1074 and 3BNC117, using deep, longitudinal sequencing of full length HIV envelope (env) genes from study participants treated with bNAb monotherapy. Improved sequencing depth and computational evolutionary analyses permit us to identify in vivo routes and parallelism underlying HIV escape from each bNAb, providing new insights into this evolutionary process: 10-1074 escape is restricted to a small number of previously documented pathways, but these escape mutations 1) pre-exist in intra-host viral populations before therapy, 2) are not all equally preferred, and 3) emerge with a high degree of genetic parallelism within and across viral populations. In contrast, 3BNC117 escape follows background-specific patterns in which specific escape mutations present in one population rarely emerge or spread in other populations, but often still exhibit parallel evolutionary responses within their host. That bNAbs elicit starkly different in vivo escape profiles depending on their Env target exposes the limitations of generalizing escape patterns across therapies and highlights the substantial challenges in predicting a viral population's bNAb susceptibility from genetic diversity alone.

Journal Article↗
PubMedDate not supplied

Adolescent mothers and their children in later life.

The popular belief that early childbearing almost certainly leads to school dropout, subsequent unwanted births and economic dependence is greatly oversimplified, if not seriously distorted: A longitudinal study of over 300 primarily urban black women who gave birth as adolescents in the middle to late 1960s shows that a substantial majority completed high school, found regular employment and, even if they had at some point been on welfare, eventually managed to escape dependence on public assistance. Relatively few ended up with large families; most had fewer births than they had wanted or expected at the time they first became pregnant. The study also found that the pathways to success were surprisingly diverse. Although young women who gave birth at an early age were disadvantaged when compared with their peers who bore children later, huge variability existed. Teenage childbearing lowered the women's likelihood of economic success and increased their likelihood of having a large family. However, the women who had more economically secure and better-educated parents were more likely to succeed--perhaps as a result of receiving a greater amount of direct aid and having other family resources available. In addition, differences in educational motivation and performance were especially important factors. Young mothers who had been doing well in school and who had had high educational aspirations at the time of their first birth were much more likely than others to be successful later. Additional births at young ages also constrained the mothers' ability to attend school and accrue job experience. Women who had more children in the five years after their first birth did less well in school, had lower aspirations and came from more disadvantaged families than did women who curtailed their fertility. However, even when such factors were controlled for, subsequent fertility lowered the chances of economic success in later life. Changes in the mothers' life courses affected some aspect of their children's behavior at all ages, but there was no simple or recurring pattern of influence. For example, a mother's welfare receipt was associated with behavior problems in her child during the preschool years, but not later on. In contrast, the mother's marital status was not related to behavior problems during the preschool period but was clearly related to such problems during the child's adolescence.

Achievement↗
PubMed2003

Alternative splicing of lola generates 19 transcription factors controlling axon guidance in Drosophila.

The Drosophila melanogaster transcription factor Lola (longitudinals lacking) is a pivotal regulator of neural wiring that sets the precise expression levels of proteins that execute specific axon guidance decisions. Lola has a zinc finger DNA binding domain and a BTB (for Broad-complex, Tramtrack and Bric a brac) dimerization motif. We now show that alternative splicing of the lola gene creates a family of 19 transcription factors. All lola isoforms share a common dimerization domain, but 17 have their own unique DNA-binding domains. Seven of these 17 isoforms are present in the distantly-related Dipteran Anopheles gambiae, suggesting that the properties of specific isoforms are likely to be critical to lola function. Analysis of the expression patterns of individual splice variants and of the phenotypes of mutants lacking single isoforms supports this idea and establishes that the alternative forms of lola are responsible for different functions of this gene. Thus, in this system, the alternative splicing of a key transcription factor helps to explain how a small genome encodes all the information that is necessary to specify the enormous diversity of axonal trajectories.

Alternative Splicing↗
PubMedDate not supplied

Genetic influences in different aspects of language development: the etiology of language skills in 4.5-year-old twins.

The genetic and environmental etiologies of diverse aspects of language ability and disability, including articulation, phonology, grammar, vocabulary, and verbal memory, were investigated in a U.K. sample of 787 pairs of 4.5-year-old same-sex and opposite-sex twins. Moderate genetic influence was found for all aspects of language in the normal range. A similar pattern was found at the low end of the distribution with the exception of two receptive measures. Environmental influence was mainly due to nonshared factors, unique to the individual, with little influence from shared environment for most measures. Genetic and environmental influences on language ability and disability are quantitatively and qualitatively similar for males and females.

Child, Preschool↗
PubMed2001

Patterns of religious practice and belief in the last year of life.

OBJECTIVES: Although it is frequently assumed that issues of religious faith become more salient at the end of life, there is little or no population-based empirical evidence testing this assumption. METHODS: Using data from the New Haven site of the Established Populations for Epidemiologic Studies of the Elderly (N = 2,812), the authors examined self-reports of attendance at services, self-ratings of religiousness, and strength and comfort felt from religion for respondents who did and did not die within 12 months following an interview. Religiousness was assessed at baseline (1982) and in follow-up interviews in 1985, 1988, and 1994. Cross-sectional comparisons of levels of religiousness were made among persons in their last 6 months of life, persons in their last 12 months of life, and persons who survived 12 months, and longitudinal comparisons were made with religiousness at the previous wave. RESULTS: After adjusting for age, sex, education, marital status, religious affiliation, and a set of health status measures, the authors found that although attendance at religious services declined among the near-deceased, this group showed either stability or a small increase in feelings of religiousness and strength/comfort received from religion. Overall levels of attendance and religious feelings were high for this religiously diverse sample. DISCUSSION: Community studies of respondents in their last year of life are rare. In this sample, religious involvement appears to continue throughout the last months of life.

Adaptation, Psychological↗
PubMed1997

The role of the msh homeobox gene during Drosophila neurogenesis: implication for the dorsoventral specification of the neuroectoderm.

Development of the Drosophila central nervous system begins with the delamination of neural and glial precursors, called neuroblasts, from the neuroectoderm. An early and important step in the generation of neural diversity is the specification of individual neuroblasts according to their position. In this study, we describe the genetic analysis of the msh gene which is likely to play a role in this process. The msh/Msx genes are one of the most highly conserved families of homeobox genes. During vertebrate spinal cord development, Msx genes (Msx1-3) are regionally expressed in the dorsal portion of the developing neuroectoderm. Similarly in Drosophila, msh is expressed in two longitudinal bands that correspond to the dorsal half of the neuroectoderm, and subsequently in many dorsal neuroblasts and their progeny. We showed that Drosophila msh loss-of-function mutations led to cell fate alterations of neuroblasts formed in the dorsal aspect of the neuroectoderm, including a possible dorsal-to-ventral fate switch. Conversely, ectopic expression of msh in the entire neuroectoderm severely disrupted the proper development of the midline and ventral neuroblasts. The results provide the first in vivo evidence for the role of the msh/Msx genes in neural development, and support the notion that they may perform phylogenetically conserved functions in the dorsoventral patterning of the neuroectoderm.

Animals↗
PubMed2026

Longitudinal whole-genome analysis of bluetongue virus identifies conserved serotype-specific genomes and distinct genomic constellations within a Colorado sheep flock (2021-2023).

Bluetongue virus (BTV) is a segmented double-stranded RNA virus of ruminants transmitted by Culicoides spp. biting midges. Although the genome consists of ten segments, classification into serotypes is primarily based on genome segment 2. However, reassortment among genomic segments is a major driver of BTV evolution and diversity. This study used longitudinal whole-genome sequencing to characterize BTV genomes collected from 2021 to 2023 within a single sheep flock in Colorado, where multiple serotypes co-circulate. Whole-genome sequences were generated from fourteen blood samples representing four serotypes: BTV-6, -11, -13, and -17. Longitudinal sampling identified multiple BTV serotypes within individual sheep across consecutive years. Tanglegram analysis comparing segment phylogenies to the segment 2 tree demonstrated incongruent topologies across all genomic segments, suggestive of reassortment or the circulation of distinct genomic constellations. Nucleotide-level comparisons revealed high sequence homology among same-serotype samples from the same year, while the greatest genetic divergence was observed among BTV-17 genomes collected in different years. Additionally, all BTV-13 genomes contained a previously undescribed nonsynonymous substitution in segment 10 predicted to extend the encoded protein by three amino acids. Together, these findings demonstrate that highly conserved BTV genomes and distinct genomic constellations can be detected at the flock level across multiple years. This longitudinal whole-genome approach reveals the genetic complexity of endemic BTV populations, including novel variants and genomic patterns consistent with reassortment that are lost with conventional serotyped-based approaches, highlighting the need to integrate whole-genome characterization into endemic BTV monitoring programs.

Animals↗
PubMedDate not supplied

Marital interactions in the process of dietary change for type 2 diabetes.

OBJECTIVE: To explore how couples adjust to dietary management of type 2 diabetes. DESIGN: Couples were interviewed, first together and then separately, during the first year after diagnosis and 1 year later. SETTING: Qualitative interviews conducted in hospital classrooms using a semistructured interview guide. PARTICIPANTS: Couples (N = 20) with a recently diagnosed spouse who met the study criteria were purposefully selected from volunteers solicited from hospital-based diabetes classes. PHENOMENON OF INTEREST: Processes used by the couple to address the prescribed diet. ANALYSIS: Thematic analysis of interview transcripts using grounded theory to identify patterns of adaptation processes used over time. RESULTS: Three couple categories emerged (cohesive, enmeshed, and disengaged), representing adaptation to the diabetic diet. Initially, 5 couples were cohesive (teamwork approach), 7 were enmeshed (nondiabetic spouse responsible for the diet; spouse was dependent), and 8 were disengaged (spouses functionally separate; spouse was solely responsible for the diet management). A year later, the majority of couples were disengaged (n = 14), 1 couple remained cohesive, and 4 couples remained enmeshed. Themes of flexibility, roles, rules, and communication varied across categories. CONCLUSIONS AND IMPLICATIONS: Understanding categories of marital adjustment to the diabetic diet may improve nutrition-based diabetes interventions. Further study is needed to verify these findings in larger and more diverse populations.

Adaptation, Psychological↗
PubMed2005

Social network diversity and risks of ischemic heart disease and total mortality: findings from the Copenhagen City Heart Study.

Measures of various types of social contacts were used as predictors of ischemic heart disease events and total mortality in an age-stratified random sample of 9,573 adults enrolled in the Copenhagen City Heart Study (Copenhagen, Denmark). Baseline examinations were conducted in 1991-1994, and participants were followed until the end of 1997. Contacts with parents, children, family members, and friends were associated with better health. The presence of a spouse or partner was protective for men. Contacts with neighbors showed a trend toward a reversed pattern, and the effects of contacts with work colleagues and children differed by gender. Most types of contacts that occurred at least monthly were just as protective as those occurring more frequently. An index of intimate social contact diversity with family and friends had graded relations with both outcomes. Comparisons of persons reporting three or more types of contacts with those reporting fewer types yielded age- and gender-adjusted hazard ratios of 0.73 (95% confidence interval (CI): 0.64, 0.82) for mortality and 0.75 (95% CI: 0.61, 0.91) for ischemic heart disease. Comparable fully adjusted hazard ratios were 0.83 (95% CI: 0.73, 0.95) and 0.82 (95% CI: 0.67, 1.00). These data suggest that health benefits are derived from the diversity of social roles, especially those involving intimate relationships.

Adult↗
PubMed2001

Parental alcoholism as a risk factor for DSM-IV-defined alcohol abuse and dependence in American women: the protective benefits of dyadic cohesion in marital communication.

Important trends in research over the past decade indicate that women are as greatly affected by familial alcoholism as are men. Although it is increasingly recognized that the adverse drinking outcomes predicted for adult children of alcoholics (COAs) are not inevitable, and only a small percentage develop alcohol dependence or grow up to be alcoholic, relatively little knowledge exists regarding moderating factors that reduce their vulnerability. This study identifies a multiple mediator latent structural model of the intergenerational transmission of risk for DSM-IV-assessed alcohol abuse and dependence among women COAs in adulthood. The effects of both parental alcoholism and family environment are estimated at three time points spanning 10 years across 5-year intervals (1984, 1989, and 1994) using data from a subsample of 4,449 women in the National Longitudinal Survey of Youth (NLSY). Dyadic cohesion in marital communication (greater marital cohesion, harmony, and less verbal disagreement, discord, and conflict) is a proposed moderating factor that may operate in adulthood to lower the risk of female COAs developing alcohol abuse and dependence. Maximum likelihood standardized estimates of the effects of alcohol mediators measured over time indicate that direct parental effects for adverse outcomes decline when COAs are in their late 20s and early 30s. Indirect parental effects through environmental influences dramatically increase the risk of abuse and dependence among COAs at this time if they have one or more alcoholic siblings, especially an alcoholic sister. Dyadic cohesion and positive interpersonal communication patterns were found to moderate effectively the relationship that existed among parental alcoholism, environmental influences, and adverse alcohol consequences. COAs with satisfactory marital communication also evidenced higher levels of intimacy with their partners, perceived the division of housework to be fairer, shared more responsibilities and burdens of the household, and had less conflict over critical domestic issues than other women COAs. The protective benefits of a good marriage against the risks of alcoholism remained when applied to younger and older subjects, across diverse backgrounds, and after adjusting for other factors such as employment status.

Adolescent↗
PubMed2026

Novel Mycoparasitic Mechanisms and Colonization Patterns on Poplar Revealed by GFP Tagging of the Biocontrol Fungus Clonostachys reniana.

Clonostachys rosea has long been the primary model for studying mycoparasitism within its genus; however, the potential of other species remains largely unexplored. In this study, we established a PEG-CaCl2-mediated protoplast transformation system for Clonostachys reniana. Our results demonstrate for the first time that this species is amenable to genetic manipulation and produces transformants with genetic stability, providing a reliable platform for functional genomic research in this fungus. Using green fluorescent protein tagging, we achieved stable transformants that retained wild-type physiological traits. Crucially, our data indicated that C. reniana utilizes a distinct mycoparasitic mechanism, which differs from the well-established sequential process of adhesion, coiling, and lysis seen in C. rosea. Confocal and scanning electron microscopy revealed that C. reniana, following initial coiling and invasive structure formation, penetrates the host hyphae of Botryosphaeria dothidea. It then grows longitudinally within the hyphal lumen, absorbing nutrients and eliminating the pathogen from the inside. Furthermore, C. reniana hyphae can colonize the intercellular spaces of the stem periderm in 84K poplar (Populus alba × P. glandulosa) while displaying a distinct tissue-specific behavior in the roots by forming a mantle on the root surface resembling that of ectomycorrhizae. These findings establish C. reniana as a highly promising secondary model species within the Clonostachys genus. By uncovering a novel "internal-consumption" mycoparasitic mode, this study expands our understanding of the ecological diversity of biocontrol fungi and provides a powerful genetic toolset for future functional genomic research.

Clonostachys reniana↗
PubMed2001

Fruit and vegetable servings in ten SENECA towns and the impact of the midday meal.

OBJECTIVE: Assessing fruit, vegetable and potato servings in relation to meal pattern. DESIGN: Longitudinal study including dietary assessment in 1988/9 and 1993. SETTING: 10 small European towns. SUBJECTS AND METHODS Counting the number of fruit, vegetable and potato servings in dietary records of 1275 men and women born 1913 to 1918. RESULTS: In the northern towns less than 12% of the subjects consumed 5 or more fruit and vegetable servings and up to 84% consumed only 2 or less servings per day. In the southern towns more than 30% consumed 5 or more servings and less than 20% had only 2 or less servings per day. In 9 of 10 towns a cooked meal at midday contained more fruit and vegetable servings than a cooked meal eaten in the evening. The weight of one serving as calculated from the regression line was 137 g for fruit, 145 g for vegetables and 196 g for potatoes. A significant relationship was found between antioxidant status and vegetables with regard to the number of servings but not to the intake in gram. CONCLUSIONS: RESULTS strengthen the hypothesis that a cooked meal at midday mediated a healthier diet than a cooked meal in the evening. Number of fruit and vegetable servings is a more accurate indication of diversity in vegetable consumption than intake in gram.

Aged↗
PubMed1994

[Acute ischemic spinal cord disease. Spinal cord infarction. A clinical study and MRI in 8 cases].

Acute spinal cord infarction (ASCI) occurs infrequently and may have diverse causes. The diagnosis of ASCI, and particularly of an anterior spinal artery syndrome (ASAS) can be confirmed nowadays by MRI, whereas in the past only necropsy confirmation was possible. Pathophysiology and long-term prognosis may be better known at present and treatments more consistent. We present the longitudinal study and clinical features of 8 patients suffering from ASCI. All of them were personally studied and had MRI examinations, often with sequential studies. three groups must be considered: one included 4 cases of ASAS at cervical level, the second 2 cases of ASAS at thoracic level and the third group with infarction of the conus medullaris (ICM), one of them developed during surgical repair of an infrarenal aortic aneurysm. Motor and sensory sequelae were assessed in each case together with possible etiological factors. In conclusion, recovery after ASAS tends to be dependent on the severity of the initial deficit. At cervical level, clinical and morphological findings argue in favour of an extrinsic selective compression of the C7 right radiculo-medullary artery as responsible for the ASA. At thoracic level, the artery preferentially occluded seems to be the sulco-commisural artery as a consequence of disc compression. Finally, an underlying peculiarity of the pattern of arterial supply is a probable predisposing factor for ICM. Generally, the long-term prognosis of ASCI is not necessarily bad.

Adult↗
PubMed2006

Longitudinal and secular trends in physical activity and sedentary behavior during adolescence.

OBJECTIVE: There is little epidemiologic research on longitudinal and secular trends in weight-related health behaviors throughout the stages of adolescence. In particular, few data are available to assess secular trends in various sedentary behaviors. The objective of this research was to investigate longitudinal and secular trends in physical activity and sedentary behavior in a large, diverse cohort of adolescents. METHODS: Project EAT-II is a 5-year longitudinal study (N = 2516) that includes 2 cohorts that allow for the observation of longitudinal changes from early to midadolescence (junior high to high school; n = 806; mean baseline age: 12.8 +/- 0.8 years) and mid- to late adolescence (high school to post-high school; n = 1710; mean baseline age: 15.8 +/- 0.8 years). EAT-II also examined secular trends in health behavior from 1999 to 2004 in midadolescence. The main outcome measures of the mixed-model regression analyses used in this research were self-reported weekly hours of moderate to vigorous physical activity, television/video viewing, and leisure-time computer use. RESULTS: Our findings indicate substantial longitudinal changes in moderate to vigorous physical activity, particularly among girls (decreasing 5.9-4.9 hours/week from early to midadolescence and 5.1-3.5 hours/week from mid- to late adolescence), and leisure-time computer use, particularly among boys (increasing 11.4-15.2 hours/week from early to midadolescence and 10.4-14.2 hours/week from mid- to late adolescence). Secular trends further indicate dramatic increases in midadolescent computer use from 1999 to 2004; girls increased from 8.8 to 11.1 hours/week, and boys increased from 10.4 to 15.2 hours/week. CONCLUSIONS: These adolescents experienced unfavorable shifts in activity patterns, such as longitudinal decreases in moderate to vigorous physical activity, coupled with longitudinal and secular increases in leisure-time computer use. Developing effective health promotion strategies that address a wide array of changing behavioral patterns will be important in promoting long-term health and active lifestyles among adolescents and young adults.

Adolescent↗
PubMed2001

Fixed, epitope-specific, cytophilic antibody response to the polymorphic block 2 domain of the Plasmodium falciparum merozoite surface antigen MSP-1 in humans living in a malaria-endemic area.

The MSP-1 merozoite surface antigen of the human malaria parasite Plasmodium falciparum is a major target of immune response. The domain called block 2 shows extensive allelic diversity, with more than 50 alleles identified, grouped into three allelic families. Presence of anti-block 2 antibodies has been associated with reduced risk for clinical malaria, but whether or not allele-specific antibodies are implicated remains unclear. To study the fine specificity of the human antibody response, we have used a series of 82 overlapping, N-biotinylated, 15-mer peptides scanning reference alleles and including numerous sequence variants. Peptide antigenicity was validated using sera from mice immunized with recombinant proteins. A cross-sectional survey conducted in a Senegalese village with intense malaria transmission indicated an overall 56 % seroprevalence. The response was specific for individuals and unrelated to the HLA type. Each responder reacted to a few peptides, unrelated to the infecting parasite genotype(s). Seroprevalence of each individual peptide was low, with no identifiable immunodominant epitope. Anti-block 2 antibodies were mostly of the IgG3 isotype, consistent with an involvement in cytophilic antibody-mediated merozoite clearance. The number of responders increased with age, but there was no accumulation of novel specificities with age and hence with exposure to an increasingly large number of alleles. A 15-month longitudinal follow up outlined a remarkably fixed response, with identical reactivity profiles, independent of the past or current parasite types, a pattern reminiscent of clonal imprinting. The implications of the characteristics of the anti-block 2 antibody response in parasite clearance are discussed.

Alleles↗