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PubMed2003

Cognitive ability and delinquent behavior among inner-city youth: a life-course analysis of main, mediating, and interaction effects.

Drawing on the emerging life-course paradigm in criminological theory, this study examines the relationship between cognitive ability and delinquent behavior within a sample of inner-city youth. The results indicate that net of statistical controls, cognitive ability maintains a robust inverse relationship with the likelihood of the onset of delinquency, the early onset of delinquency, and the persistence of delinquency during the 18-year period covered by the dataset. Furthermore, cognitive ability mediates the effect of concentrated disadvantage on both the onset and early onset of delinquency. Overall, the results of this study suggest that cognitive ability is an important criminogenic risk factor that has important implications for both correctional interventions and the continued development of structural and multilevel theories of crime.

Adolescent↗

PubMed2005

Comparison of a spatial approach with the multilevel approach for investigating place effects on health: the example of healthcare utilisation in France.

STUDY OBJECTIVE: Most studies of place effects on health have followed the multilevel analytical approach that investigates geographical variations of health phenomena by fragmenting space into arbitrary areas. This study examined whether analysing geographical variations across continuous space with spatial modelling techniques and contextual indicators that capture space as a continuous dimension surrounding individual residences provided more relevant information on the spatial distribution of outcomes. Healthcare utilisation in France was taken as an illustrative example in comparing the spatial approach with the multilevel approach. DESIGN: Multilevel and spatial analyses of cross sectional data. PARTICIPANTS: 10,955 beneficiaries of the three principal national health insurance funds, surveyed in 1998 and 2000 on continental France. MAIN RESULTS: Multilevel models showed significant geographical variations in healthcare utilisation. However, the Moran's I statistic showed spatial autocorrelation unaccounted for by multilevel models. Modelling the correlation between people as a decreasing function of the spatial distance between them, spatial mixed models gave information not only on the magnitude, but also on the scale of spatial variations, and provided more accurate standard errors for risk factors effects. The socioeconomic level of the residential context and the supply of physicians were independently associated with healthcare utilisation. Place indicators better explained spatial variations in healthcare utilisation when measured across continuous space, rather than within administrative areas. CONCLUSIONS: The kind of conceptualization of space during analysis influences the understanding of place effects on health. In many contextual studies, viewing space as a continuum may yield more relevant information on the spatial distribution of outcomes.

Adult↗

PubMed2005

Event-related potentials related to normal and morphed emotional faces.

S. Bentin and L. Y. Deouell (2000) have suggested that face recognition is achieved through a special-purpose neural mechanism, and its existence can be identified by a specific event-related potential (ERP) correlate, the N170 effect. In the present study, the authors explored the structural significance of N170 by comparing normal vs. morphed stimuli. They used a morphing procedure that allows a fine modification of some perceptual details (first-order relations). The authors also aimed to verify the independence of face identification from other cognitive mechanisms, such as comprehension of emotional facial expressions, by applying an emotion-by-emotion analysis to examine the emotional effect on N170 ERP variation. They analyzed the peak amplitude and latency variables in the temporal window of 120-180 ms. The ERP correlate showed a classic N170 ERP effect, more negative and more posteriorly distributed for morphed faces compared with normal faces. In addition, they found a lateralization effect, with a greater right-side distribution of the N170, but not directly correlated to the morphed or normal conditions. Two cognitive codes, structural and expression, are discussed, and the results are compared with the multilevel model proposed by V. Bruce and A. W. Young (1986, 1998).

Adult↗

PubMed1996

The role of surveillance in the hierarchy of prevention.

Surveillance is the collection, analysis, and dissemination of results for the purpose of prevention. Surveillance tells us what our problems are, how big they are, where the solutions should be directed, how well (or poorly) our solutions have worked, and if, over time, there is improvement or deterioration. Surveillance is essential to successful sustained public health intervention for the purposes of prevention. Surveillance systems must be tailored to the specific disease or injury that is to be prevented. Surveillance should not be limited to the occurrence of death, disease, or disability. Public health is a multilevel cascade of activities involving recognition, evaluation, and intervention. Public health should include elements of experimentation as well as field implementation with evaluation. Surveillance is the mechanism to modify any element in the cascade based upon that element's contribution to prevention or lack thereof. Any element in the causal or intervention pathway is appropriate for surveillance as long as the monitoring of the element is useful in improving the prevention system. These elements include the occurrence of hazard and intervention as well as disease, death, or disability. Examples will be provided that demonstrate the roles of surveillance in the recognition of new diseases, the evaluation of the persistence of recognized problems, the estimation of the magnitude and trends of public health problems, and the provision of information to motivate intervention.

Persons with Disabilities↗

PubMed2005

High performance liquid chromatography analysis of a 4-anilinoquinazoline derivative (PD153035), a specific inhibitor of the epidermal growth factor receptor tyrosine kinase, in rat plasma.

The quinazoline derivative, 4-N-(3'-bromo-phenyl)amino-6,7-dimethoxyquinazoline (PD153035), has recently been identified as a potential drug for the treatment of proliferative disease. Here, we report a sensitive high performance liquid chromatography (HPLC)-based quantitative detection method for measurement of PD153035 levels in rat plasma. Sample pretreatment involved a two-step extraction with chloroform. The analytes were separated on a column packed with OmniSpher C18 material and eluted with acetonitrile-0.1 M ammonium acetate, pH 7.2 (70:30, v/v). The column effluent was monitored by UV detection at 330 nm. A linear response was achieved over the concentration range 0.50-100.00 microM using multilevel calibration with an internal standard. The analytical method inter- and intra-run accuracy and precision were better than +/-15%. The lower limit of quantification was 0.50 microM. The method has been applied to study the preclinical pharmacokinetics of this compound in rats.

Animals↗

PubMed2006

Use of health care services by ethnic minorities in The Netherlands: do patterns differ?

BACKGROUND: This article examines the nature of ethnic differences in health care utilisation by assessing patterns of use in addition to single service utilisation. METHODS: Data were derived from the Second Dutch National Survey of General Practice. A nationally representative sample of 104 general practices participated in this survey. Data on health and health service utilisation were collected through face-to-face interviews. Based on a random sample per practice, a total of 12 699 Dutch-speaking people were interviewed, regardless of ethnic background. An additional study among a random sample of 1339 people from the four largest minority groups in The Netherlands was conducted. These four groups comprised people from Turkey, Surinam, Morocco, and The Netherlands Antilles. Multilevel analyses were performed to investigate ethnic differences in health care utilisation, adjusting for socio-economic status, health status, and level of urbanisation. RESULTS: Differences in utilisation patterns were particularly marked for people with a Moroccan, Turkish, or Antillean background. Compared to the other groups, Surinamese were more likely to have had contact with any professional health care service. No evidence was found that the gate keeping role of general practitioners in The Netherlands functions less effectively among the ethnic minority groups as compared to the indigenous population. CONCLUSION: The analysis of patterns of utilisation proved to supply useful information concerning the relationship between ethnicity and use of health care services in addition to figures concerning single service use only.

Adolescent↗

PubMed2000

A meta-analysis of case-control and cohort studies with interval-censored exposure data: application to chorionic villus sampling.

Chorionic villus sampling (CVS) is a valued method of prenatal diagnosis that is often preferred over amniocentesis because it can be performed earlier, but which has also raised concern over a possible association with increased risk of terminal transverse limb deficiency (TTLD). We present and apply a meta-analytic method for estimating a combined dose-response effect from a series of case-control and cohort studies in which the exposure variable is interval-censored. Assuming coarsening at random for the interval-censoring, and calling upon the familiar result of Cornfield to pool case-control and cohort information on the association between a rare binary outcome and a multilevel exposure variable, we form a likelihood-based model to assess the effect of gestational age at the time of CVS on the presence or absence of a rare birth defect. Effect estimates are computed with a variant of the EM algorithm termed the method of weights, which enables the use of standard weighted regression software. Our findings suggest that CVS exposure at early gestational age leads to an increased risk of TTLD.

Journal Article↗

PubMed2000

A biomechanical, radiologic, and clinical comparison of outcome after multilevel cervical laminectomy or laminoplasty in the rabbit.

STUDY DESIGN: A rabbit model was used to compare clinical outcome, radiographic changes, and biomechanical flexibility after cervical laminectomy and open-door laminoplasty. OBJECTIVE: This study tested the hypothesis that radiographic changes and biomechanical flexibility could explain the differences in clinical outcome after cervical laminectomy and laminoplasty. SUMMARY OF BACKGROUND DATA: Although multilevel cervical laminoplasty is thought to have advantages over cervical laminectomy, clinical outcome studies have been contradictory, and no experimental study has examined the possible mechanisms for the differences after healing. METHODS: Twenty-four New Zealand White rabbits were randomized into four groups: normal, sham, C3-C6 wide laminectomy, and C3-C6 open-door laminoplasty. Clinical, radiographic, and biomechanical data were collected and compared up to 3 months after surgery. RESULTS: Laminectomy had a statistically significant poorer clinical outcome when compared with laminoplasty after 3 months of healing. Radiologic analysis showed statistically significant angular deformity in the laminectomy group compared with laminoplasty and control groups at 3 months. In contrast, biomechanical measures of flexibility, neutral zone, and range of motion showed only small differences between any of the groups at any time. CONCLUSIONS: The presence of deformity, and not a change in flexibility, is responsible for the differences in clinical outcome observed after laminectomy compared with laminoplasty in this model.

Animals↗

PubMed2002

Respiratory dysfunction in patients with chronic-onset cervical myelopathy.

STUDY DESIGN: A retrospective study. OBJECTIVE To clarify the characteristics of respiratory dysfunction associated with chronic-onset cervical myelopathy. SUMMARY OF BACKGROUND DATA: In acute cervical cord injury, respiratory dysfunction, especially vital capacity (VC), is impaired, which causes respiratory complications. No comprehensive study has been published about respiratory dysfunction in patients with chronic-onset myelopathy. METHODS: Eighty-four consecutive patients without history of respiratory disease who underwent surgery for cervical myelopathy were studied. The control group consisted of 84 age-matched patients with lumbar degenerative diseases. Parameters of spirometry, arterial blood gas, height of the diaphragm, and the score for neurologic impairment were analyzed before and after surgery. RESULTS: Percent VC (%VC) was significantly lower in the study group than in the control group. In patients with cranial cord lesions and multilevel cord lesions, %VC was lower than in those with a caudal lesion and a single-level lesion, respectively. Percent VC correlated with the preoperative neurologic score in the study group. In patients having the lesion at or above C4, %VC improved after surgery, whereas in those with a lower lesion, %VC had not decreased before surgery, and no further improvement was obtained. CONCLUSIONS: In patients with chronic-onset cervical myelopathy, %VC significantly decreases when they have more cranial or multilevel lesions. Percent VC also correlates with the preoperative neurologic score and improves with surgical treatment in patients with more cranial cord lesions. Respiratory dysfunction should be taken into consideration as a part of neurologic impairment in chronic-onset cervical myelopathy.

Chronic Disease↗

PubMed1999

Loosening at the screw-vertebra junction in multilevel anterior cervical plate constructs.

STUDY DESIGN: An in vitro biomechanical study of one-level and three-level corpectomy and anterior cervical plate models. OBJECTIVE: To investigate the failure of the screw-vertebra interfaces in one- and three-level corpectomy models. SUMMARY AND BACKGROUND DATA: Although there are several biomechanical studies of strength and stability of anterior cervical plating, there has been no investigation into clinically observed failures. METHODS: One- and three-level models (corpectomy, strut graft, and anterior plate) were constructed from eight cadaveric specimens (C2-T1). Multidirectional flexibility tests (1.0 Nm moments) performed before and after fatigue (1000 cycles, 1.0 Nm flexion-extension, 0.14 Hz) documented the screw-vertebra motions at upper and lower ends. Ranges of motion and neutral zones were determined. Analysis of variance was used to evaluate significant differences between the upper and lower ends of the plates and changes caused by fatigue loading (P < 0.05). RESULTS: Extension motion at the lower ends was more than at the upper ends in both models. Fatigue increased three-level model ranges of motion at the lower end by 171% in flexion, 164% in extension, 153% in lateral bending, and 115% in axial rotation. Similar increases were observed in neutral zones. Fatigue loading produced no significant changes in one-level models. CONCLUSION: There was excessive screw-vertebra motion caused by fatigue at the lower end of the three-level corpectomy model. These findings of loosening may explain clinically observed failures at the caudal end of long anterior cervical plate constructs. Longer screws, larger diameter screws, and supplemental posterior fixation may decrease screw-vertebra loosening.

Biomechanical Phenomena↗

PubMed2026

Multilevel Exploration of Shared Genetic Architecture Between Primary Biliary Cholangitis and Four Autoimmune Diseases.

INTRODUCTION: Primary Biliary Cholangitis (PBC) frequently coexists with various autoimmune diseases, such as Multiple Sclerosis (MS), Psoriasis (PS), Rheumatoid Arthritis (RA), and Sjögren's Syndrome (SS). Understanding the genetic associations between these diseases is crucial for providing deeper insights into their shared pathogenic mechanisms and comorbidity patterns. METHODS: This study utilized genome-wide association study summary data of PBC and four autoimmune diseases (MS, PS, RA, and SS). A multi-stage analytical pipeline was employed to systematically investigate the genetic associations between the diseases. The analytical approach consisted of three stages: first, linkage disequilibrium score regression and high-definition likelihood methods were applied to estimate overall genetic correlations between the diseases; second, local genetic correlation analysis was conducted to pinpoint genetic signals in specific chromosomal regions; third, conditional/conjunctional false discovery rate (cond/conjFDR) algorithms were used to quantitatively assess genetic overlap and identify shared susceptibility loci. RESULTS: Genome-wide analysis revealed significant genetic associations between PBC and the four autoimmune diseases (MS, PS, RA, and SS). Regional analysis showed local genetic correlations across various chromosomal segments. cond/conjFDR analysis confirmed genetic intersections among the diseases and identified several critical genetic polymorphic loci that influence disease susceptibility. DISCUSSION: This study comprehensively delineates the shared genetic architecture underlying PBC and four autoimmune diseases through integrative analyses of multiple genome-wide approaches. The results highlight strong genetic correlations, particularly between PBC and MS, PS, RA, and SS, and identify key shared susceptibility genes, including CLEC16A, CD58, CD86, STAT4, IRF5, TYK2, and TNFAIP3, which collectively mediate immune dysregulation through autophagy, cytokine signaling, and NF-κB pathways. These findings not only extend current understanding of the molecular mechanisms driving autoimmune comorbidity but also provide potential genetic targets for future functional validation and therapeutic exploration. CONCLUSION: This study provides comprehensive genomic evidence for the genetic connections between PBC and the four autoimmune diseases (MS, PS, RA, and SS), offering valuable insights into the shared pathological mechanisms underlying their comorbidities.

Humans↗

PubMed2006

Ex vivo sentinel lymph node mapping in colon cancer: improving the accuracy of pathologic staging?

BACKGROUND: A subset of patients with colon cancer staged by conventional methods have occult micrometastases and do not receive adjuvant chemotherapy. Sentinel lymph node (SLN) mapping and staining by immunohistochemistry is a technique that may identify such occult micrometastases, thereby upstaging patients with positive findings. The purpose of this study was to determine whether ex vivo SLN mapping in colon cancer could be applied successfully to patients at our institution. METHODS: Seventeen patients with intraperitoneal colon tumors undergoing resection were studied prospectively. SLNs were identified as the first blue stained node(s) after ex vivo peritumoral injection of isosulfan blue dye. Additional lymph nodes were harvested and processed in accordance with standard pathologic evaluation for colon cancer. All nodes were examined after routine hematoxylin and eosin (H&E) staining. SLNs that were negative on H&E were analyzed further by multilevel sectioning and immunohistochemistry staining using anticytokeratin monoclonal antibody. RESULTS: Of the 17 study patients, SLNs were identified in 16 (94%) cases. The SLN was the only positive node in 3 patients. An identified SLN was positive (by H&E) in all patients with associated positive non-SLN nodes. The average number of nodes retrieved per patient was 16 (range, 4-54). Overall, SLNs accurately reflected the status of the entire lymph node basin in 16 (94%) patients. Two (12%) patients with negative nodes by H&E potentially were upstaged after further SLN analysis. The negative predictive value for SLN mapping was 89%. CONCLUSIONS: The ex vivo technique of SLN mapping for colon cancer is feasible. In the current study, SLN results were concordant with non-SLNs in the majority of patients. Furthermore, this technique may have upstaged 2 (12%) patients. Whether this ultimately will affect overall survival has yet to be determined.

Adenoma, Villous↗

PubMed2024

Sulfonamide-induced DNA hypomethylation disturbed sugar metabolism in rice (Oryza sativa L.).

DNA methylation is well-accepted as a bridge to unravel the complex interplay between genome and environmental exposures, and its alteration regulated the cellular metabolic responses towards pollutants. However, the mechanism underlying site-specific aberrant DNA methylation and metabolic disorders under pollutant stresses remained elusive. Herein, the multilevel omics interferences of sulfonamides (i.e., sulfadiazine and sulfamerazine), a group of antibiotics pervasive in farmland soils, towards rice in 14 days of 1 mg/L hydroponic exposure were systematically evaluated. Metabolome and transcriptome analyses showed that 57.1-71.4 % of mono- and disaccharides were accumulated, and the differentially expressed genes were involved in the promotion of sugar hydrolysis, as well as the detoxification of sulfonamides. Most differentially methylated regions (DMRs) were hypomethylated ones (accounting for 87-95 %), and 92 % of which were located in the CHH context (H = A, C, or T base). KEGG enrichment analysis revealed that CHH-DMRs in the promoter regions were enriched in sugar metabolism. To reveal the significant hypomethylation of CHH, multi-spectroscopic and thermodynamic approaches, combined with molecular simulation were conducted to investigate the molecular interaction between sulfonamides and DNA in different sequence contexts, and the result demonstrated that sulfonamides would insert into the minor grooves of DNA, and exhibited a stronger affinity with the CHH contexts of DNA compared to CG or CHG contexts. Computational modeling of DNA 3D structures further confirmed that the binding led to a pitch increase of 0.1 Å and a 3.8° decrease in the twist angle of DNA in the CHH context. This specific interaction and the downregulation of methyltransferase CMT2 (log2FC = -4.04) inhibited the DNA methylation. These results indicated that DNA methylation-based assessment was useful for metabolic toxicity prediction and health risk assessment.

DNA Methylation↗

PubMed2006

The significance of neighbourhood context to child and adolescent health and well-being: a systematic review of multilevel studies.

Growing up in a poor neighbourhood has negative effects on children and adolescents. In the literature it has been concluded that the risk of low birth weight, childhood injury and abuse, and teenage pregnancy or criminality double in poor areas. However, the validity of such studies has been questioned, as they have been associated with ecological or individualistic fallacies. Studies using multilevel technique might thus contribute important knowledge in this field. The present review clarifies the importance of neighbourhood contextual factors in child and adolescent health outcomes, through considering only studies using multilevel technique. Keyword searching of the Medline, ERIC, PsycInfo, Sociological Abstracts, and Social Citation Index databases was performed. Original studies using multilevel technique to examine the effect of neighbourhood characteristics on child and adolescent health outcomes, and focusing on populations in high-income countries were included. Neighbourhood socioeconomic status and social climate were shown to have small to moderate effects on child health outcomes, i.e. birth weight, injuries, behavioural problems, and child maltreatment. On average, 10% of variation in health outcomes was explained by neighbourhood determinants, after controlling for important individual and family variables. This review demonstrates that interventions in underprivileged neighbourhoods can reduce health risks to children, especially in families that lack resources. An analysis of methodological fallacies indicates that observed effects and effect sizes can be underestimated, and that interventions may well have greater impact than this review was able to establish.

Adolescent↗

PubMed2006

Rapid growth among term children whose birth weight was appropriate for gestational age has a longer lasting effect on body fat percentage than on body mass index.

BACKGROUND: It is not clear whether and how rapid growth in infancy, a risk factor for later obesity, differentially affects growth and body-composition development throughout childhood in term children with an appropriate-for-gestational age (AGA) birth weight. OBJECTIVE: The aim was to examine the effect of rapid growth in infancy on body mass index SD score (BMI SDS) and body fat percentage (%BF) trajectories until age 7 y. DESIGN: This analysis included 206 (50.5% female) AGA term participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Repeated anthropometric measurements were obtained between 0.5 and 7 y of age. RESULTS: Fifty-nine of the 206 children (28.6%) displayed rapid growth (an increase in SDS for weight of >0.67 between birth and age 2 y). From 6 mo of age, their growth trajectories diverged from normal growers, and by age 7 y they had a higher BMI, more fat mass, and a higher risk of overweight (odds ratio: 6.2; 95% CI: 2.4, 16.5; P = 0.0002). Multilevel model analyses showed that the differences in BMI were achieved within the first 2 y of life [beta (+/-SE) SDS: 1.22 +/- 0.13], after which they persisted at this level until the age of 7 y, whereas differences in %BF, which were also already discernible by age 2 y (1.52 +/- 0.34%), became progressively larger over the next 5 y (adjusted difference: 0.23 +/- 0.11%/y; P = 0.03). CONCLUSIONS: Rapid growth in infancy and early childhood results in an increased BMI and %BF throughout childhood and an increased risk of overweight at age 7 y among AGA children. Rapid growth in AGA children has a more pronounced effect on %BF than on BMI.

Adipose Tissue↗

PubMed1999

[Surgical treatment of injuries of the thoracolumbar transition. 1: Epidemiology].

The authors report on a prospective multicenter study with regard to the operative treatment of fractures and dislocations of the thoracolumbar spine. 18 traumatologic centers in Germany and Austria, forming the working group "spine" of the German Society of Trauma Surgery, are participating in this continuing study. Between September 1994 and December 1996 682 patients (64% male) with an average age of 39 1/2 (7-83) years were entered. The entry criteria included all patients with acute and operatively treated (within 3 weeks after trauma) fractures and dislocations of the thoracolumbar spine (Th 10-L 2). Part 1 of this publication outlines the protocol and epidemiologic data. The incidence of fractures and dislocations of the thoracolumbar spine and associated injuries were recorded according to a standardized protocol, as well as the different operative methods and complications, duration of hospital stay, rehabilitation and incapacity. The analysis of the clinical social and radiological course was a second focus. The most frequent mechanism of injury was a fall (50%) or traffic accident (22%). Most of the fractures occurred at the L 1 level (49%). All injuries were classified according to the ASIF (AO) classification. 65% sustained an A-type fracture (compression fracture). Associated injuries were observed in 35% and 6% were polytraumatized. Extremities and thorax were most frequently affected. Younger age and traffic accidents lead more often to C-type fracture (fracture dislocation) and polytrauma. An increased number of multisegmental or multilevel lesions were observed in polytraumatized patients. There were 16% with incomplete paraplegia (Frankel/ASIA B-D) and 5% with complete paraplegia (Frankel/ASIA A). The rate of patients with initial neurologic deficits significantly increased with the severity of spinal injury according to the Magerl classification. Until discharge a neurologic improvement (at least 1 Frankel/ASIA grade) was observed in 32% of the partially paralyzed (Frankel/ASIA B-D) and in 12% of the patients with complete paraplegia (Frankel/ASIA A). A neurologic deterioration occurred in 3 patients (0.4%). As a base for further follow-up and late results the individual starting point was determined by collecting relevant data of the patients' history: 277 (40.6%) patients suffered from simultaneous diseases, one half was spine related. At the time of injury 559 (82.0%) patients were employed; 429 (62.9%) doing manual work. 369 (54.1%) patients stated sportive activities before the injury and 561 (82.3%) designated their "back function" as normal. For the time before injury the patients scored an average of 93.4 points in the Hannover Spine Score (0-100 points concerning complaints and function of the back/spine).

Adolescent↗

PubMed2002

Mental activity during sleep.

Since remote antiquity humankind has believed in the supernatural origin of dreaming. The scientific approach to mental activity during sleep dates back to the eighteenth century. One hundred years ago, psychoanalysis introduced dream analysis for diagnostic and therapeutic purposes. Only 50 years ago psychophysiology made it possible to collect mental sleep activity by means of experimental awakenings while monitoring physiological variables; this approach encouraged investigation into the relationship between the features of sleep activity and sleep state (REM versus NREM). Advances in neurophysiology, in neurochemistry, and recently in brain imaging techniques, have shed light on the roles played by the different cerebral structures in determining specific characteristics of mental activity during sleep. The development of cognitive psychology has enabled investigation of dream generation in terms of output from a complex multilevel system of information processing. In addition to sleep state, other factors, such as the time of the night and the sequence of the NREM-REM cycles, have been shown to influence the characteristics of mental activity. The usefulness of investigation of mental sleep activity as a clinical tool is controversial. The psychophysiological approach to mental sleep activity in clinical contexts has enabled the exploration of adaptation processes and contributed to neuropsychological studies on focal and systemic brain pathology.

Brain↗

PubMed1997

Establishement of the dorso-ventral pattern during embryonic development of drosophila melanogasater: a logical analysis

This report focuses on dorso-ventral patterning in the segmented region of the Drosophila melanogaster embryo. According to the concept of positional information, this pattern results from the different response of cells to the Dorsal-protein morphogen. This protein shows a distribution gradient along the dorso-ventral axis, with the highest concentration on the ventral side. Using the generalized logical formalism developed by R. Thomas and co-workers, the different cellular responses were analysed in terms of the intracellular loops between the regulatory genes. Two positive loops were found to be involved, each constituting a switch which can be acted upon by the Dorsal morphogen to determine the different cell types that make up the embryonic dorso-ventral pattern. The novelty in this use of generalized logical formalism is the employment of a multilevel variable to represent a morphogen gradient. The proposed model accounts for the essential qualitative effects of the Dorsal gradient in the dorso-ventral determination process. Three main conclusions may be drawn. Firstly, the gene twist needs to have two functional threshold concentrations, one for autoactivation and the other for activation of the gene snail. Secondly, the autoactivation threshold must be smaller than that which activates snail. Thirdly, the action of the gene snail on the maintenance function of the gene twist is crucial for cells to be able to choose between the mesoderm or neuroectoderm developmental pathways. Furthermore, it is predicted that if the gene snail shows autoregulation, this will not be crucial for the determination of the embryonic D-V pattern. Copyright 1997 Academic Press Limited Copyright 1997 Academic Press Limited

Journal Article↗