Prediction of potential thermostable proteins in Xylella fastidiosa.

The average protein (E+K)/(Q+H) ratio in organisms has already been demonstrated to have a strong correlation with their optimal growth temperature. Employing the Thermo-Search web tool, we used this ratio as a basis to look for thermostable proteins in a mesophile, Xylella fastidiosa. Nine proteins were chosen to have their three-dimensional structures modeled by homology, using mainly proteins from mesophiles as templates. Resulting models featured a high number of hydrophobic interactions, a property that has been previously associated with thermostability. These results demonstrate the interesting possibility of using the (E+K)/(Q+H) ratio to find individual thermostable proteins in mesophilic organisms.

Neuropsychological and functional cognitive skills of 35 unselected adults with sex chromosome abnormalities.

This report presents data defining the neuropsychological and cognitive phenotypes of a group of adults with sex chromosome abnormalities identified at birth through the chromosome screening of 40,000 consecutive newborns between 1964 and 1974. In all three nonmosaic groups, reading skills were impaired and intelligence quotients were on average reduced more than 20 points relative to controls. The 47,XXX women demonstrated greatest overall impairment, including reduced scores on tests of conceptualization and problem solving. 45,X women demonstrated impairment in spatial thinking skills, and 47,XXY men in verbal processing skills. No reduced scores were found in the female mosaic group. Marked variability in scores was seen in all groups; some propositi have been unable to hold any job, whereas others have completed college and are professionally employed.

Life adaptation in 35 adults with sex chromosome abnormalities.

PURPOSE: This report from the last phase of the 36-year Denver Study provides information about the adult life adaptation of 35 men and women with sex chromosome abnormalities (SCA) followed since their identification at birth. METHODS: Sex chromatin screening of 40,000 consecutive newborns between 1964 and 1974 resulted in the cohort of 35 SCA men and women followed to date since birth. Sixteen chromosomally normal siblings served as controls. Data constituting this report was obtained from formal and informal interviews and psychological testing conducted in the final year of this study. RESULTS: The nonmosaic SCA propositi had lower mean intelligence quotients and psychosocial adjustment scores than did siblings. Consistent with these results, propositi also had lower levels of educational achievement and career success, although most have completed school, married, hold full-time employment, and are financially independent. CONCLUSIONS: While the SCA adults demonstrated lower levels of cognitive and psychosocial competence, their overall adaptation has been positive, particularly given an early literature suggesting a high rate of psychopathology and severe dysfunction.

Effects of glufosinate-ammonium on off crop vegetation--interim results.

In 2000 a field study was conducted at four different locations concerning the effects of low dosages of glufosinate-ammonium, a leaf acting herbicide, on off crop vegetation. Therefore species rich road verges and ditch banks not adapted to a history of herbicide use were sprayed twice with different dosages of glufosinate-ammonium, simulating drift (0, 2, 4, 16, 32 and 64% of the maximum field dose: 800 g a.i./ha). The parameters studied were short term phytotoxic effects and the effects on biomass, species cover and number of species in autumn (Braun-Blanquêt relevés). The results show significant phytotoxic effects at all dosages of glufosinate-ammonium on the non-target vegetation. The low concentrations (2 and 4%) had most impact when applied early in the season (9% average at the 2% dosage and 22% at 4% dosage, after the first spraying. At high dosages (32 and 64%) a decrease of the biomass of the vegetation was found in August. A comparison between treatments in August shows a small decrease in species number and cover in the 64% compared to the control. In the comparison between the spring and August relevés, the decrease in the mean number of species was significantly stronger in the treated plots than in the untreated ones of 4% and higher. For monocotyledons in all treatments except 16%, a significantly stronger decrease in species number was found compared to the untreated. For dicotyledons only the 64% dosage differed from the untreated. Only at the 64% treatment the total cover of species decreased more than in the untreated plots. Since drift percentages of 2-4% can be expected at 1-2 m from a treated plot it can be concluded that the use of glufosinate-ammonium could result in visible short term phytotoxic effects (max 22%) on off-crop vegetation such as ditch banks and verges. There are also indications that effects on the number and cover of species in autumn can occur. Because in future glufosinate-ammonium could be used on a large scale in herbicide resistant crops like maize, which will be cultivated on the same field for many years, this study will be continued in 2001 in order to investigate if there are--whether or not--sustainable effects on the off crop vegetation.

Brain morphology in Klinefelter syndrome: extra X chromosome and testosterone supplementation.

OBJECTIVE: This study focuses on variation in brain morphology associated with supernumerary X chromosome and Klinefelter syndrome (KS). Using an unselected birth cohort of KS subjects and high-resolution MRI, the authors investigated the neuroanatomic consequences of the 47,XXY karyotype in the presence and absence of exogenous testosterone supplementation. METHODS: Regional brain volumes were measured in 10 subjects with KS and 10 age-matched control men. Five of the KS subjects had received testosterone supplementation since puberty (KS+T) and five had not (KS-T). RESULTS: KS subjects showed significant (p < 0.01) reduction in left temporal lobe gray matter volumes compared with normal control subjects. Differences in left temporal gray volumes were also significant between the KS+T and KS-T groups (p < 0.01). Verbal fluency scores were significantly different between the KS+T and KS-T groups as well. CONCLUSION: Supernumerary X chromosome material in men is associated with a reduction in left temporal lobe gray matter, a finding that is consistent with the verbal and language deficits associated with KS. Also, relative preservation of gray matter in the left temporal region is associated with exposure to exogenous androgen during development. A history of testosterone supplementation also appears to be associated with increased verbal fluency scores in KS patients.

Psychosocial competence of unselected young adults with sex chromosome abnormalities.

Very little is known about the adult adaptation of individuals with sex chromosome abnormalities (SCA) except for a few reports based upon biased samples of clinically identified patients. This first report from the Denver SCA study on the adult psychosocial adaptation of 36 unselected propositi, identified at birth, shows a continuation of mild psychological and social problems. Psychiatric interviews and self-reported information revealed that adaptation is quite variable, with many of the nonmosaic propositi not faring as well as their siblings, but in a few instances exceeding the success of brothers and sisters. Within this group of SCA subjects a subset demonstrated more marked pathology and a tendency to over-rate their social adaptation relative to the psychiatric interviewer, suggesting that the exclusive use of self-report questionnaires may not provide accurate assessment of psychological characteristics in this and other special populations. The full adult SCA behavioral phenotype has not yet been established but is emerging through additional reports from this and other studies of unselected SCA adults.

Compound heterozygous female with fragile X syndrome.

We report on a 15-year-old compound heterozygous young woman with fragile X syndrome who has a full mutation of 363 repeats on one X chromosome and a premutation of 103 repeats on the other X chromosome. As predicted, subsequent testing demonstrated that her father carries a premutation (98 repeats) as does her mother (146 repeats). There is only one previous report of a compound heterozygous female with fragile X syndrome. By quantitation of Southern blot signals, the activation ratio for the premutation (the proportion of the premutation on the active X chromosome) was determined to be 0.78. Immunocytochemistry of blood smears showed fragile X mental retardation-1 protein (FMRP) expression in 63.5% of lymphocytes. Cognitively, this woman is functioning in the mid-range of involvement for fragile X females. She attends regular classes and receives supplemental assistance for her learning disabilities. She experiences behavior characteristics typical of females with fragile X syndrome including severe shyness, anxiety, panic episodes, mood swings, and attention deficits. She has responded very well to appropriate treatment including fluoxetine for anxiety, methylphenidate for attentional problems, and educational therapy.

Transition from adolescence to early adulthood: adaptation and psychiatric status of women with 47,XXX.

OBJECTIVE: To investigate the adolescent and early adult adaptation of a group of 47,XXX women as compared with their siblings, addressing developmental differences in adaptation and psychiatric status. METHOD: Subjects included eleven 47,XXX women and nine female sibling controls. Interviews during adolescence and during early adulthood were semistructured and included a psychiatric evaluation. Four areas of inquiry were (1) relationships with other family members, (2) sense of self-esteem, (3) sexual identity and preference, and (4) responses to life stressors. A DSM-IV psychiatric diagnosis was assigned where appropriate. The Schedule for Affective Disorders and Schizophrenia-Lifetime version was also administered, and assessments of overall functioning and adaptation were completed. RESULTS: The 47,XXX women during adolescence and young adulthood were less well adapted; had more stress; had more work, leisure, and relationship problems; had a lower IQ; and showed more psychopathology when contrasted with the comparison group. However, most of the 47,XXX women were self-sufficient and functioning reasonably well, albeit less well than their siblings. CONCLUSIONS: This longitudinal study has clarified that previously reported outcomes of severe psychopathology and antisocial behavior in individuals with sex chromosome anomalies are rare and variability in the behavioral phenotype is much larger than originally appreciated.

Intrauterine diagnosis of sex chromosome aneuploidy.

OBJECTIVE: To provide current information on sex chromosome aneuploidies to obstetricians who encounter such diagnoses and who counsel prospective parents faced with the prenatal diagnosis of a sex chromosome aneuploidy. DATA SOURCES: Unbiased information about the natural course of sex chromosome aneuploidy has become available only in the last few years. Current knowledge is based on seven prospective studies on unselected individuals with sex chromosome aneuploidy identified 20-30 years ago. All literature on sex chromosome aneuploidy was reviewed. Karyotypes specifically addressed included the following: 47,XXY, 47,XXX, 47,XYY, 45,X, 45,X/46,XX, 46,XX/47,XXX, and 46,XY/47,XXY. METHODS OF STUDY SELECTION: The international studies followed the affected subjects from birth to young adulthood. All published reports, case studies, and articles were reviewed. TABULATION, INTEGRATION, AND RESULTS: All prospective studies were included in the course of determining necessary information for obstetricians and prospective parents. Points addressed for each of the aneuploid karyotypes included expected phenotype, reproductive competence, developmental risks, and intervention therapies. CONCLUSION: Information about sex chromosome aneuploidy can assist obstetricians in providing accurate and comprehensive genetic counseling to parents of affected fetuses, and thereby facilitate the process of making an informed decision about pregnancy management.

Sex chromosome tetrasomy and pentasomy.

Sex chromosome abnormalities occur in at least 1 in 400 births and include the well-described 47,XXX, 47,XXY, 47,XYY, and 45,X karyotypes. The addition of more than one extra X or Y chromosome occurs rarely, and little information is available in the medical literature. Individual case reports make up most of this body of knowledge, and all are based on subjects who identified themselves postnatally. Many were ascertained through screenings of institutions and hospitals; thus, there is no unbiased information on the natural history of poly X and Y karyotypes. A direct relationship between the number of additional sex chromosomes and the severity of the phenotype is generally assumed. The purpose of this article is to summarize what is known about these conditions and to present 10 additional cases. The karyotypes include, 48,XXXX, 49,XXXXX, 48,XXYY, 48,XXXY, 49,XXXXY, 49,XXXYY, 48,XYYY, 49,XYYYY, and 49,XXYYY.

Psychosocial adaptation of 39 adolescents with sex chromosome abnormalities.

OBJECTIVES: Children with sex chromosome abnormalities (SCA) are known to be at increased risk for neuromotor, language, learning, and behavioral problems, but little is known of psychosocial adaptation of SCA adolescents. This study was conducted to evaluate psychologic characteristics of unselected SCA adolescents, including socialization, educational progress, separation from family, and incidence and severity of psychiatric disturbance. METHODS: Thirty-nine propositi identified through the screening of 40,000 consecutive Denver newborns, including boys with 47,XXY karyotypes and girls with 47,XXX, 45,X, and partial X monosomy, or SCA mosaic karyotypes, have been followed longitudinally into adolescence. Twenty-seven siblings served as controls. Between 12 and 19 years of age, all participated in blind psychiatric interviews and were administered standardized intelligence and achievement tests. RESULTS: SCA propositi demonstrated a mean IQ score 21 points lower than that of control subjects. In addition, lower mean scores were seen on achievement test results as well as lower overall psychosocial adaptation scores and increased incidence of psychiatric disturbance. Depression was the most frequent psychiatric diagnosis. Propositi were more likely to receive special education assistance in high school and were less likely to graduate from high school than were controls. Of the three nonmosaic propositi groups, the 47,XXX girls demonstrated the poorest overall psychosocial adaptation and highest degree of psychiatric disturbance. Mosaic girls were indistinguishable from control subjects. Marked variability was found among all three nonmosaic groups, with some individuals in each group demonstrating relatively strong psychosocial adaptation. CONCLUSIONS: The presence of nonmosaic sex chromosome abnormality increases the risk for impeded cognitive skills, learning abilities, and psychosocial adaptation in adolescence. The factors that allow for stronger adaptation in some of these adolescents include the presence of a stable and supportive family environment. The outlook for adaptation in unselected SCA adults remains uncertain.

Neuropsychological impairment in 42 adolescents with sex chromosome abnormalities.

Sixty-seven adolescents participated in this protocol, including 42 with sex chromosome abnormalities and 25 controls. Results from a battery of neuropsychological tests indicated karyotype specific patterns of neuropsychological impairment: (1) 47,XXY boys had unimpaired intelligence but reduced abilities in verbal fluency and reading; (2) 47,XXX girls experienced reduced general intelligence accompanied by impaired scores on individual tests of attention, concept formation, spatial thinking, verbal fluency, and academic skills, while retention of memorized information was a relative strength; (3) among the 45,X girls average intelligence level was also reduced along with scores on tests of attention, concept formation, verbal fluency, spatial thinking, and academic skills, and an atypical pattern of hand dominance was identified; (4) test scores in the group of mosaic females did not differ from those of controls. Test scores and patterns of personal adaptation were quite variable in all groups; while eight nonmosaic propositi required intensive special education assistance in their public schooling, eight others have attended college.

Prognosis of prenatally diagnosed children with sex chromosome aneuploidy.

Sex chromosome aneuploidy (SCA) occurs in about 1/250 amniocenteses, and the significance of the long-term prognosis of fetuses with SCA is of concern to prospective parents and health care providers. Longitudinal studies in an unselected group of newborn infants with SCA diagnosed postnatally have refuted allegations of mental retardation but have documented an increased risk for developmental problems. Of the 530 phone consultations with parents faced with a prenatal diagnosis of SCA, 68% continued the pregnancy. Twenty of the oldest subsequently born children (now 7-14 years old) were available for follow-up. In this small sample and age group, the propositi are progressing developmentally at a rate comparable to their sibs and are doing better at school and in peer relations than the SCA group diagnosed postnatally. Only 2 have documented IQs as low as 90. The documented IQs of the remainder, none of whom are sex chromosome mosaics, are all over 110. The parent population in this prenatally diagnosed group is unique and different from that of the postnatally diagnosed group in that over 85% of them are college graduates, often professionals, and upper socioeconomic individuals. The developmental competence of this SCA sample may be attributable to the supportive environment provided by these families, all of whom made a conscious decision to continue the pregnancy.

Decisions following the intrauterine diagnosis of sex chromosome aneuploidy.

This is a report of 327 phone calls to our center concerning the intrauterine diagnosis of sex chromosome abnormalities (SCA). The first author (A.R.) responded to each by counseling either the parents or the referring professional. Sixty-two percent continued the pregnancy. When the parents were counseled directly, the percentage continuing the pregnancy was significantly higher than when the information was transmitted through the professionals. Our results are different from most reports in these situations, and suggest that well-informed couples, counseled by geneticists, are more likely to continue these pregnancies. The possible occurrence of SCA should be considered in preamniocentesis counseling.

Gross and fine motor development in 45,X and 47,XXX girls.

Neuromuscular deficits have been described in 47,XXY and 47,XYY boys, but gross and fine motor development of girls with sex chromosome aneuploidy has not been extensively studied. Twenty-one propositae 8 to 19 years of age, identified through newborn screening to be 45,X, 47,XXX, or 45,X mosaic, and 11 control girls were evaluated by a physical therapist unaware of their genetic constitution. The Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) was administered, and the quality of neuromuscular function was determined. The 45,X and 47,XXX propositae exhibited both gross and fine motor dysfunction, with 12 of 15 BOTMP composite scores below the 10th percentile. The clinical assessment confirmed the BOTMP findings, with 13 propositae exhibiting dysfunctional sensory-motor integration. A delay in the age of independent walking confirmed the consistency of motor developmental dysfunction throughout time. Sex chromosome mosaics were more similar to control girls. The gross and fine motor delays were frequently associated with a moderate to severe language dysfunction which adversely affected classroom performance. Regular developmental assessments of children with sex chromosome aneuploidy, including sensory-motor integration, should assist in the identification of early developmental delays and permit appropriate intervention.

Verbal and spatial processing efficiency in 32 children with sex chromosome abnormalities.

Spatial and linguistic processing efficiency was evaluated in sixty 8- to 18-yr-old children, including thirteen 47,XXY boys, eleven 47,XXX girls, six girls with 45,X, two girls with 46,X,Xq-, and 28 chromosomally normal controls. Results indicated that the 47,XXX girls performed significantly below controls on all four cognitive tests. Scores of the X monosomy group were reduced on both spatial tests, one requiring rapid information processing and one without time requirements, which is consistent with previous reports of spatial thinking deficits in these propositae. The X monosomy girls also had difficulty completing the high efficiency but not the low efficiency verbal tests. Scores in the 47,XXY group did not differ from controls on either spatial test or on the low efficiency verbal task. When required to rapidly access verbal information from memory, however, the performance of these boys was significantly impaired. This finding confirms earlier reports of impeded verbal fluency in these propositi. Alteration in capacity to rapidly process information appears to distinguish 47,XXY boys and X monosomy girls from their chromosomally normal peers, and suggests that adaptations in their educational setting should be introduced to allow additional time to learn and complete work.

47,XXX: what is the prognosis?

Eleven unselected 47,XXX girls, now 15 to 22 years of age, have been observed from birth in a prospective study of children with sex chromosome anomalies. A description of their growth and development is presented. The 47,XXX infants were not generally distinguishable from chromosomally normal children in the first year of life, even though there was a slight delay in neuromotor development. By 2 years of age, developmental delays in speech and language often became evident, and speech therapy was often necessitated in the preschool years. Early school problems included speech and language deficiencies, lack of coordination, poor academic performance, and immature behavior; these persisted throughout the school years. By high school age, a 47,XXX girl was generally tall and often subject to somatic complaints. Sexual development was generally normal. Seven of the 11 propositae had a diagnosed psychiatric disorder or disturbance at some time during adolescence. Variability within this syndrome is great; one proposita is in college and another is mentally retarded. The frequency of the diagnosis of the 47,XXX karyotype by genetic amniocentesis is estimated to be 1/1000, the same incidence as in the newborn population. Expectant parents must be counseled as to the significance of this karyotype and prognostic information must be given. Suggested guidelines are included.