A case‐control study of brain structure and behavioral characteristics in 47,XXX syndrome

Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under‐recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age‐ and sex‐matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi‐structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention‐deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population‐based studies of Trisomy X and also found in our sample.     

Role of viral envelope sialic acid in membrane fusion mediated by the vesicular stomatitis virus envelope glycoprotein.

Fusion of vesicular stomatitis virus (VSV) with cells and liposomes before and after treatment with neuraminidase was studied using the R18 dequenching assay. Desialylation of VSV significantly enhanced the extent of fusion with Vero cells but affected neither the pH dependence nor the binding of VSV to Vero cells. The enhanced fusion of asialo-VSV was observed both at the plasma membrane as well as via the endocytic pathway. Both VSV and asialo-VSV fused with liposomes made of neutral phospholipid, but only asialo-VSV fused with liposomes containing a 1:1 mixture of neutral and negatively charged phospholipid. To examine factors which contribute to the extent of fusion, we analyzed the various activation and inactivation reactions that take place as a result of low-pH triggering of VSV prebound to the target membrane. Lag times for the onset of fusion were similar for VSV and asialo-VSV, indicating that desialylation did not affect the activation reactions. However, exposure of VSV bound to target membranes at pH 6.5 for 400 s led to considerable inactivation, whereas little inactivation was seen after desialylation of VSV. These results are analyzed in terms of a model which allows us to determine which components of the overall fusion process are dominated by viral envelope sialic acid.     

The C- and the N-terminal regions of glycoprotein 41 ectodomain fuse membranes enriched and not enriched with cholesterol, respectively

To infect target cells, HIV-1 employs a virally encoded transmembrane protein (gp41) to fuse its viral envelope with the target cell plasma membrane. We describe the gp41 ectodomain as comprised of N- and C-terminal subdomains, each containing a heptad repeat as well as a fusogenic region, whose organization is mirrored by the intervening loop region. Recent evidence indicates that the gp41 directed fusion reaction proceeds to initial pore formation prior to gp41 folding into its low energy hairpin conformation. This implies that exposed regions of the gp41 ectodomain are responsible for the bulk of the fusion work, probably through direct protein-membrane interactions. Prevalent fusion models contend that the gp41 ectodomain initially interacts with the target cell surface through its highly hydrophobic N terminus, which is believed to insert into the target membrane, thereby linking the virus to the target cell. This arrangement allows the N-terminal subdomain to interact with the target cell surface, whereas the C-terminal subdomain remains proximal to the virion, allowing interaction with the viral envelope. The composition of the viral envelope and the target cell surface differ due to the virus budding from raft microdomains. We show here that constructs corresponding to the C-terminal subdomain specifically destabilize ordered and cholesterol rich membranes (33 molar %), whereas the N-terminal subdomain is more effective in fusing both unordered cholesterol-free membranes and those containing lower amounts of cholesterol (10 molar %). Moreover we show that, in the context of the C-terminal subdomain, the heptad repeat contributes helical structure, which may describe the enhanced inhibitory effect of the C-terminal subdomain relative to the C-terminal heptad repeat (C34) alone. Our results are discussed in light of recent findings that showcase the role of exposed gp41 regions in effecting membrane fusion.     

Unique molecular markers in human endometriosis: implications for diagnosis and therapy

Endometriosis originates in the uterine lining and affects ~20% of reproductive-age women. The disease often causes chronic pelvic pain, affects ovulatory function and influences fertility. Although laparoscopic diagnosis of uterine endometriosis is quite specific, direct visualisation can be difficult or inaccurate in some circumstances, and it is not useful for diagnosing extra-abdominal disease. Laparoscopy is an invasive procedure, has significant morbidity and cannot be carried out frequently to monitor efficacy of therapy and the possibility of recurrence. Thus, a specific, non-invasive diagnostic test is required. One intriguing area of research uses the technology of radioimmunotargeting, which has previously been used for cancer detection. This technique could have potential for the specific detection and eventual treatment of endometriosis. A marker, eosinophil peroxidase (EPO), has been identified that is expressed in ~90% of endometriosis specimens, and is not expressed or only weakly expressed in normal endometrium. The US Food and Drug Administration has approved a monoclonal antibody to EPO for investigation as an immunoimaging agent in cancers that exhibit eosinophilia. EPO targeting using this antibody could be useful for detecting and/or treating endometriosis.     

Spectral correspondence between visual spectral sensitivity and bioluminescence emission spectra in the click beetle Pyrophorus punctatissimus (Coleoptera: Elateridae)

The presence of two spectral mechanisms, near-ultraviolet and green (lambda(max)=545nm), is strongly suggested by electroretinographic visual spectral sensitivity curves obtained under dark and red chromatic adaptation conditions in the compound eyes of the click beetle Pyrophorus punctatissimus. The bioluminescence emission of the dorsal prothoracic lanterns is deep green (lambda(max)=543nm) and that of the ventral abdominal lantern is lime green (lambda(max)=556nm) in colour in P. punctatissimus. A broad green visual receptor would detect both deep green and lime green bioluminescent optical signals.     

Interactions between resource availability and enemy release in plant invasion

Understanding why some exotic species become invasive is essential to controlling their populations. This review discusses the possibility that two mechanisms of invasion, release from natural enemies and increased resource availability, may interact. When plants invade new continents, they leave many herbivores and pathogens behind. Species most regulated by enemies in their native range have the most potential for enemy release, and enemy regulation may be strongest for high-resource species. High resource availability is associated with low defence investment, high nutritional value, high enemy damage and consequently strong enemy regulation. Therefore, invasive plant species adapted to high resource availability may also gain most from enemy release. Strong release of high-resource species would predict that: (i) both enemy release and resources may underlie plant invasion, leading to potential interactions among control measures; (ii) increases in resource availability due to disturbance or eutrophication may increase the advantage of exotic over native species; (iii) exotic species will tend to have high-resource traits relative to coexisting native species; and (iv) although high-resource plants may experience strong enemy release in ecological time, well-defended low-resource plants may have stronger evolutionary responses to the absence of enemies.     

Evaluation and optimization of a vibrotactile signal in an autonomous driving context

An important issue in autonomous vehicle development is the transition phase between autonomous and manual driving. Here, we focused on a vibrotactile signal that warns the driver 1 min before they must take over. Our goal was to design a signal detectable by, and satisfactory for, all drivers. After listing parameters defining a vibrotactile signal, we performed a design‐of‐experiments study to select 16 signals for evaluation by 80 participants of different ages, body mass indexes, and genders. In a car on the road, autonomous driving conditions were simulated with the participant in the front passenger seat, who performed a task unrelated to driving. Whenever the participant detected a signal, they gave a satisfaction score. Modeling enabled us to evaluate the effects of the signal parameters and participant characteristics on satisfaction and detection. Moreover, we obtained specifications for the design of a tactile signal according to our two criteria.

Practical applications

To the best of our knowledge, this is the first study to focus on the sensory aspect of a tactile signal in a car environment. Both functional (i.e., signal detection) and hedonic aspects are important. We investigated the influence of gender, age, and body mass index of the participants on signal detection and satisfaction score, and optimized the satisfaction score under detection constraints. We use a 3‐point method to reach those two goals:

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Advantage of combining NLCQ-1 (NSC 709257) with radiation in treatment of human head and neck xenografts

NLCQ-1 (NSC 709257), a hypoxia-selective cytotoxin that targets DNA through weak intercalation, was investigated for efficacy in combination with single or fractionated radiotherapy of human head and neck xenografts. A staged tumor experiment was performed in tumor-bearing female athymic nude mice that were locally irradiated with or without NLCQ-1. Tumor hypoxia was assessed by immunohistochemistry for pimonidazole adducts in tumors of varying weight. Fractionated radiation, depending on the dose, was administered either once daily for 4 days or once daily for 4 days followed by a 7-day rest and repeat. NLCQ-1 was administered i.p. at 15 mg/kg alone or 45 min before each radiation dose. Hypoxia (1-52%) was detected in all tumors and was positively correlated with tumor size. NLCQ-1 alone resulted in about 10 days of tumor growth delay, measured at sixfold the tumor's original size, without causing toxicity. All combination treatments with NLCQ-1 were more effective than treatments with radiation alone. Radiation at 1 Gy given once daily for 4 days on days 20 and 30 caused 3.5 days of tumor growth delay, whereas in combination with NLCQ-1 it caused 14.5 days of growth delay. Radiation at 5 Gy given in two doses 10 days apart resulted in 3.5 days of tumor growth delay, whereas more than 20 additional days of delay were observed in combination with NLCQ-1. Radiation given as a single dose of 10 Gy resulted in about 7 days of tumor growth delay, whereas in combination with NLCQ-1 about 30 additional days of delay were seen. These results suggest a significant advantage in combining radiation with NLCQ-1 in treatment of human head and neck tumors, which are known to have hypoxic areas.     

Ten-Year Trends in Coronary Calcification in Individuals without Clinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis

Background

Coronary heart disease (CHD) incidence has declined significantly in the US, as have levels of major coronary risk factors, including LDL-cholesterol, hypertension and smoking, but whether trends in subclinical atherosclerosis mirror these trends is not known.

Methods and Findings

To describe recent secular trends in subclinical atherosclerosis as measured by serial evaluations of coronary artery calcification (CAC) prevalence in a population over 10 years, we measured CAC using computed tomography (CT) and CHD risk factors in five serial cross-sectional samples of men and women from four race/ethnic groups, aged 55–84 and without clinical cardiovascular disease, who were members of Multi-Ethnic Study of Atherosclerosis (MESA) cohort from 2000 to 2012. Sample sizes ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the prevalence of CAC increased across exams among African Americans, whose prevalence of CAC was 52.4% in 2000–02, 50.4% in 2003–04, 60.0% is 2005–06, 57.4% in 2007–08, and 61.3% in 2010–12 (p for trend <0.001). The trend was strongest among African Americans aged 55–64 [prevalence ratio for 2010–12 vs. 2000–02, 1.59 (95% confidence interval 1.06, 2.39); p = 0.005 for trend across exams]. There were no consistent trends in any other ethnic group. Risk factors generally improved in the cohort, and adjustment for risk factors did not change trends in CAC prevalence.

Conclusions

There was a significant secular trend towards increased prevalence of CAC over 10 years among African Americans and no change in three other ethnic groups. Trends did not reflect concurrent general improvement in risk factors. The trend towards a higher prevalence of CAC in African Americans suggests that CHD risk in this population is not improving relative to other groups.