Genetic analyses of maternal and teacher ratings on attention problems in 7-year-old Dutch twins

The goal of the present study is to examine genetic and environmental influences on maternal and teacher ratings of Attention Problems (AP) in 7-year-old children. Teachers completed the Teacher Report Form (N=2259 pairs), and mothers the Child Behavior Checklist (N=2057 pairs). Higher correlations were found in twins rated by the same teacher than in twins rated by different teachers. This can be explained by rater bias or by a greater environmental sharing in twins, who are in the same classroom. We further found that 41% of the variation in maternal and teacher ratings is explained by a common factor. The heritability of this common factor is 78%. The heritabilities of the rater specific factors of mothers and teachers are 76% and 39%, respectively. Because Attention Problems that are persistent over situations may indicate more serious behavior problems than context dependent Attention Problems, we believe that gene finding strategies should focus on this common phenotype

Genetic and environmental influences on the relation between attention problems and Attention Deficit Hyperactivity Disorder.

Objective: The assessment of symptoms of ADHD in children is usually based on a clinical interview or a behavior checklist. The aim of the present study is to investigate the extent to which these instruments measure an underlying construct and to estimate the genetic and environmental influences on individual differences in ADHD. Methods: Maternal ratings were collected on 10,916 twins from 5,458 families. Child Behavior Checklist (CBCL) ratings were available for 10,018, 6,565, and 5,780 twins at the ages 7, 10, and 12, respectively. The Conners Rating Scale (4,887 twins) and the DSM interview (1,006 twins) were completed at age 12. The magnitude of genetic and environmental influences on the variance of the three measures of ADHD and the covariance among the three measures of ADHD was obtained. Results: Phenotypic correlations range between .45 and .77. Variances and covariances of the measurements were explained mainly by genetic influences. The model that provided the best account of the data included an independent pathway for additive and dominant genetic effects. The genetic correlations among the measures collected at age 12 varied between .63 and 1.00. Conclusions: The genetic overlap between questionnaire ratings and the DSM-IV diagnosis of ADHD is high. Clinical and research implications of these findings are presented

Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness

<p>Abstract</p> <p>Background</p> <p>Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (R_min) is abnormally elevated in subjects with airway hyperresponsiveness.</p> <p>Methods</p> <p>The R_minwas measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. R_minand spirometric indices were measured before and after bronchodilation (albuterol) and bronchoconstriction (methacholine). A preliminary study of 84 healthy subjects first established height dependence of baseline R_minvalues.</p> <p>Results</p> <p>Asthmatics had a higher baseline R_min% predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004). Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline R_minwas able to identify subjects with airway hyperresponsiveness (PC₂₀< 16 mg/mL) better than most spirometric indices (Area under curve = 0.85, 0.78, and 0.87 for R_min% predicted, FEV₁% predicted, and FEF_25-75% predicted, respectively). Also, 80% of the subjects with baseline R_min< 100% predicted did not have airway hyperresponsiveness while 100% of subjects with R_min> 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic.</p> <p>Conclusions</p> <p>These findings suggest that baseline R_min, a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline R_minto asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, R_mincould provide a clinically useful tool for assessing asthma and monitoring response to treatment.</p

Mental health among clients of the Sydney Medically Supervised Injecting Centre (MSIC)

The Sydney Medically Supervised Injecting Centre (MSIC) is a supervised injecting facility (SIF) where people who inject drugs (PWID) can do so legally, under health professional supervision. The majority of clients have low levels of education and employment, high rates of incarceration and unstable housing and poor social networks, and 70 % do not access local health services. These factors increase the risk of poor mental health, and it has been documented that PWID have elevated rates of mood, anxiety, personality and psychotic disorders; post-traumatic stress disorder (PTSD); and higher rates of trauma exposure, suicidality and self-harm. The current study is the first to investigate the mental health among clients of a SIF. Validated instruments to examine clients’ mental health, social networks and trauma histories were administered to 50 frequently attending clients by a mental health nurse. The majority of respondents were unemployed, homeless and had a history of incarceration, and 82 % report they had been diagnosed with a mental health problem, but only 24 % report they were receiving treatment. Respondents had poor social networks, had poorer mental health symptoms compared to US inpatients and had experienced multiple traumatic events, and a high number of respondents had scores indicative of PTSD. These results highlight the need for mental health clinicians to be employed in SIFs and other drug consumption rooms (DCRs) to assist clients to address their mental health and psychosocial needs, particularly in light of the fact that these services are often the only places these PWID engage with in an ongoing way

Bacteria are important dimethylsulfoniopropionate producers in marine aphotic and high-pressure environments

Dimethylsulfoniopropionate (DMSP) is an important marine osmolyte. Aphotic environments are only recently being considered as potential contributors to global DMSP production. Here, our Mariana Trench study reveals a typical seawater DMSP/dimethylsulfide (DMS) profile, with highest concentrations in the euphotic zone and decreased but consistent levels below. The genetic potential for bacterial DMSP synthesis via the dsyB gene and its transcription is greater in the deep ocean, and is highest in the sediment.s DMSP catabolic potential is present throughout the trench waters, but is less prominent below 8000 m, perhaps indicating a preference to store DMSP in the deep for stress protection. Deep ocean bacterial isolates show enhanced DMSP production under increased hydrostatic pressure. Furthermore, bacterial dsyB mutants are less tolerant of deep ocean pressures than wild-type strains. Thus, we propose a physiological function for DMSP in hydrostatic pressure protection, and that bacteria are key DMSP producers in deep seawater and sediment

The Water Bugs (Heteroptera: Nepomorpha) of the Guyana Region

NEPOMORPHA OF THE GUYANA REGION The Nepomorpha of the Guyana Region are keyed out and described. In addition distributional, faunistical and comparative notes on the species are given. New species and subspecies: Ochterus aeneifrons surinamensis, O. tenebrosus; Limnocoris fittkaui surinamensis; Ranatra adelomorpha; Neoplea globoidea; Buenoa amnigenopsis; Tenagobia pseudoromani from Suriname and Ranatra ornitheia from Guyana. New synonyms (junior ones between parenthesis): Gelaslocorus flavus flavus Guér. (G. nebulosus nebulosus Guér.); Pelocoris impicticollis Stål (P. horváthi Mont.), P. poeyi (Guér.) not identical with P. femoratus (P.-B.) (P. convexus Nieser), P. procurrens White (P. minutus Mont.); Belostoma bicavum Lauck ( B. parvoculum Lauck); Ranatra doesburgi De Carlo (R. usingeri De C.), R. macrophthalma H.-S. (R. surinamensis De C.), R. mediana Mont. (R. williamsi Kuitert), R. obscura Mont. (R. annulipes White 1879 not Stål), R. sarmentoi De C. (R. ameghinoi De C.); Buenoa amnigenopsis n. sp. ( B. amnigenus Nieser 1968, 1970 not White), B. amnigenus (White) (B. amnigenoidea Nieser 1970), B. nitida Truxal (B. doesburgi Nieser); Heterocorixa surinamensis Nieser ( H. boliviensis Nieser 1970 not Hungerford); Tenagobia incerta Lundbl. ( T. signata and T. serrata in part, Nieser 1970 not White and Deay respectively), T. socialis (White) (T. serrata in part, Nieser 1970 not Deay)

G-Quadruplex DNA Sequences Are Evolutionarily Conserved and Associated with Distinct Genomic Features in Saccharomyces cerevisiae

G-quadruplex DNA is a four-stranded DNA structure formed by non-Watson-Crick base pairing between stacked sets of four guanines. Many possible functions have been proposed for this structure, but its in vivo role in the cell is still largely unresolved. We carried out a genome-wide survey of the evolutionary conservation of regions with the potential to form G-quadruplex DNA structures (G4 DNA motifs) across seven yeast species. We found that G4 DNA motifs were significantly more conserved than expected by chance, and the nucleotide-level conservation patterns suggested that the motif conservation was the result of the formation of G4 DNA structures. We characterized the association of conserved and non-conserved G4 DNA motifs in Saccharomyces cerevisiae with more than 40 known genome features and gene classes. Our comprehensive, integrated evolutionary and functional analysis confirmed the previously observed associations of G4 DNA motifs with promoter regions and the rDNA, and it identified several previously unrecognized associations of G4 DNA motifs with genomic features, such as mitotic and meiotic double-strand break sites (DSBs). Conserved G4 DNA motifs maintained strong associations with promoters and the rDNA, but not with DSBs. We also performed the first analysis of G4 DNA motifs in the mitochondria, and surprisingly found a tenfold higher concentration of the motifs in the AT-rich yeast mitochondrial DNA than in nuclear DNA. The evolutionary conservation of the G4 DNA motif and its association with specific genome features supports the hypothesis that G4 DNA has in vivo functions that are under evolutionary constraint

Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia.The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity.S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with models for receptor activation in which ligand-binding or T-ALL-associated mutations lead to conformational changes of the NRR that permit metalloprotease cleavage

Female genital schistosomiasis as an evidence of a neglected cause for reproductive ill-health: a retrospective histopathological study from Tanzania

BACKGROUND: Schistosomiasis affects the reproductive health of women. Described sequelae are ectopic pregnancy, infertility, abortion, and cervical lesions and symptoms mimicking cervical cancer and STIs. There are indications that cervical schistosomiasis lesions could become co-factors for viral infection such as HIV and HPV. METHODS: In a retrospective descriptive histopathological study clinical specimens sent between 1999 and 2005 to the pathology department of a consultant hospital in Tanzania were reviewed to analyse the occurrence and features of schistosomiasis in female genital organs. RESULTS: During the study period, schistosomiasis was histopathologically diagnosed in 423 specimens from different organs (0.7% of all specimens examined in the study period), out of those 40% were specimens from female and male organs. The specimens were sent from 24 hospitals in 13 regions of mainland Tanzania. Female genital schistosomiasis was diagnosed in 125 specimens from 111 patients. The main symptoms reported were bleeding disorders (48%), ulcer (17%), tumor (20%), lower abdominal pain (11%) and infertility (7%). The majority of cases with genital schistosomiasis were diagnosed in cervical tissue (71 cases). The confirmation of cervical cancer was specifically requested for 53 women, but the diagnosis could only be verified for 13 patients (25%), in 40 cases only severe cervical schistosomiasis was diagnosed. Vulval/labial schistosomiasis was seen in specimens from young women. Infertility was reported in four patients with schistosomiasis of the Fallopian tubes. CONCLUSION: Genital schistosomiasis adds to the disease burden of women in all age groups. Pathological consequences due to the involvement of different genital organs can be damaging for the affected women. Clinical unawareness of genital schistosomiasis can lead to misdiagnosis and therefore false and ineffective therapy. In endemic areas cervical schistosomiasis should be considered as differential diagnosis of cancer