The distribution of distinct integrins in focal contacts is determined by the substratum composition

The distribution of two integrins, the fibronectin receptor and the vitronectin receptor, has been explored in an endothelium-derived cell line plated onto various substrata. On a fibronectin substratum, in the presence of serum, these cells develop focal contacts that contain the fibronectin receptor, whereas the vitronectin receptor is diffusely distributed over the cell surface. Conversely, cells plated onto vitronectin-coated coverslips concentrate only the vitronectin receptor within focal contacts. The accumulation of the vitronectin receptor within focal contacts also occurs when the cells are plated on uncoated coverslips but in the presence of serum. Therefore, we conclude that under normal culture conditions (i.e. in serum-containing media), the vitronectin receptor is the predominant form of integrin involved in substratum adhesion. This conclusion is supported by experiments in which cells were cultured on fibronectin-coated coverslips in the presence of serum. Initially these cells developed focal contacts containing only the fibronectin receptor. Within several hours, however, there was a progressive replacement of focal contacts containing the fibronectin receptor by focal contacts expressing the vitronectin receptor. After approximately 12 h in culture, most cells contained focal contacts expressing only the vitronectin receptor. Focal contacts containing either the fibronectin or vitronectin receptor were both associated with the termini of stress fibres and contained the proteins talin and vinculin. These observations lead us to propose that the cell does not discriminate between these different integrins when assembling the cytoskeletal components at the cytoplasmic face of focal contacts

Central Versus Peripheral Cardiovascular Risk in Metabolic Syndrome

Individuals with metabolic syndrome (MetS; i.e., three of five of the following risk factors (RFs): elevated blood pressure, waist circumference, triglycerides, blood glucose, or reduced HDL) are thought to be prone to serious cardiovascular disease and there is debate as to whether the disease begins in the peripheral vasculature or centrally. This study investigates hemodynamics, cardiac function/morphology, and mechanical properties of the central (heart, carotid artery) or peripheral [total peripheral resistance (TPR), forearm vascular bed] vasculature in individuals without (1–2 RFs: n = 28), or with (≥3 RFs: n = 46) MetS. After adjustments for statin and blood pressure medication use, those with MetS had lower mitral valve E/A ratios (<3 RFs: 1.24 ± 0.07; ≥3 RFs: 1.01 ± 0.04; P = 0.025), and higher TPR index (<3 RFs: 48 ± 2 mmHg/L/min/m2; ≥3 RFs: 53 ± 2 mmHg/L/min/m2; P = 0.04). There were no differences in heart size, carotid artery measurements, cardiovagal baroreflex, pulse-wave velocity, stroke volume index, or cardiac output index due to MetS after adjustments for statin and blood pressure medication use. The use of statins was associated with increased inertia in the brachial vascular bed, increased HbA1c and decreased LDL cholesterol. The independent use of anti-hypertensive medication was associated with decreased predicted VO2max, triglycerides, diastolic blood pressure, interventricular septum thickness, calculated left ventricle mass, left ventricle posterior wall thickness, and left ventricle pre-ejection period, but increased carotid stiffness, HDL cholesterol, and heart rate. These data imply that both a central cardiac effect and a peripheral effect of vascular resistance are expressed in MetS. These data also indicate that variance in between-group responses due to pharmacological treatments are important factors to consider in studying cardiovascular changes in these individuals

Cross-beam energy transfer in conditions relevant to direct-drive implosions on OMEGA

In cross-beam energy transfer (CBET), the interference of two laser beams ponderomotively drives an ion-acoustic wave that coherently scatters light from one beam into the other. This redirection of laser beam energy can severely inhibit the performance of direct-drive inertial confinement fusion (ICF) implosions. To assess the role of nonlinear and kinetic processes in direct-drive-relevant CBET, the energy transfer between two laser beams in the plasma conditions of an ICF implosion at the OMEGA laser facility was modeled using particle-in-cell simulations. For typical laser beam intensities, the simulations are in excellent agreement with linear kinetic theory, indicating that nonlinear processes do not play a role in direct-drive implosions. At higher intensities, CBET can be modified by pump depletion, backward stimulated Raman scattering, or ion trapping, depending on the plasma density

Negative Impressions of Childbirth in a North-West England Student Population

Background: Socio-cultural childbirth representations can influence perceptions of childbirth negatively. In this paper we report on a survey study to explore factors associated with negative impressions of childbirth in a North-West England University student sample. We also explored whether different sources and perceptions of childbirth information were linked to fear of childbirth. Methods: All students received a survey link via an online messaging board and/or direct email. Female students who were 18-40 years of age and childless (but planned to have children in the future) were invited to participate. Demographics, birth preferences, a fear of birth and general anxiety measures were included as well as questions about what sources of information shaped students’ attitudes towards pregnancy and birth (i.e. visual/written media, experiences of friends/family members, school-based education, and other) and impressions of birth from these sources (i.e. positive, negative, both positive and negative and not applicable). Results: Eligible students (n=276) completed the online questionnaire. The majority were Caucasian (87%) with a mean age of 22.6 years. Ninety-two students (33.3%) reported negative childbirth impressions through direct or vicarious sources. Students with negative impressions were significantly more likely to report higher fear of birth scores. Negatively perceived birth stories of friends/family members, and mixed perceptions of visual media representations of birth were associated with higher fear of birth scores. Having witnessed a birth first-hand and describing the experience as amazing was linked to lower fear scores. Conclusion: First-hand observations of birth, especially positive experiences, had implications for salutary outcomes. Negative or conflicting perceptions of vicarious experiences were associated with increased levels of childbirth fear. While further research is needed, these 3 insights suggest a need for positive birth stories and messages to be disseminated to mitigate negative effects of indirect accounts

Detection of Native-State Nonadditivity in Double Mutant Cycles via Hydrogen Exchange

Proteins have evolved to exploit long-range structural and dynamic effects as a means of regulating function. Understanding communication between sites in proteins is therefore vital to our comprehension of such phenomena as allostery, catalysis, and ligand binding/ejection. Double mutant cycle analysis has long been used to determine the existence of communication between pairs of sites—proximal or distal—in proteins. Typically, non-additivity (or “thermodynamic coupling”) is measured from global transitions in concert with a single probe. Here, we have applied the atomic resolution of NMR in tandem with native-state hydrogen exchange (HX) to probe the structure/energy landscape for information transduction between a large number of distal sites in a protein. Considering the event of amide proton exchange as an energetically quantifiable structural perturbation, m n-dimensional cycles can be constructed from mutation of n-1 residues, where m is the number of residues for which HX data is available. Thus, efficient mapping of a large number of couplings is made possible. We have applied this technique to one additive and two non-additive double mutant cycles in a model system, eglin c. We find heterogeneity of HX-monitored couplings for each cycle, yet, averaging results in strong agreement with traditionally measured values. Furthermore, long-range couplings observed at locally exchanging residues indicate that the basis for communication can occur within the native state ensemble, a conclusion which is not apparent from traditional measurements. We propose that higher-order couplings can be obtained and show that such couplings provide a mechanistic basis for understanding lower-order couplings, via “spheres of perturbation”. The method is presented as an additional tool for identifying a large number of couplings with greater coverage of the protein of interest

Evaluation of midkine and anterior gradient 2 in a multimarker panel for the detection of ovarian cancer

The aims of this study were: to characterise and compare plasma concentrations of midkine (MDK) in normal healthy women with concentrations observed in women with ovarian cancer; and to establish and compare the performance of MDK with that of anterior gradient 2 protein (AGR2) and CA125 in the development of multi-analyte classification algorithms for ovarian cancer. Median plasma concentrations of immunoreactive MDK, AGR2 and CA125 were significantly greater in the case cohort (909 pg/ml, 765 pg/ml and 502 U/ml, respectively n = 46) than in the control cohort (383 pg/ml, 188 pg/ml and 13 U/ml, respectively n = 61) (p < 0.001). The area under the receiver operator characteristic curve (AUC) for MDK and AGR2 was not significantly different (0.734 ± 0.046 and 0.784 ± 0.049, respectively, mean ± SE) but were both significantly less than the AUC for CA125 (0.934 ± 0.030, p < 0.003). When subjected to stochastic gradient boosted logistic regression modelling, the AUC of the multi-analyte panel (MDK, AGR2 and CA125, 0.988 ± 0.010) was significantly greater than that of CA125 alone (0.934 ± 0.030, p = 0.035). The sensitivity and specificity of the multi-analyte algorithm were 95.2 and 97.7%, respectively. Within the study cohort, CA125 displayed a sensitivity and specificity of 87.0 and 94.6%, respectively. The data obtained in this study confirm that both MDK and AGR2 individually display utility as biomarkers for ovarian cancer and that in a multi-analyte panel significantly improve the diagnostic utility of CA125 in symptomatic women

Activity, specificity and structure of I-Bth0305I: a representative of a new homing endonuclease family

Novel family of putative homing endonuclease genes was recently discovered during analyses of metagenomic and genomic sequence data. One such protein is encoded within a group I intron that resides in the recA gene of the Bacillus thuringiensis 0305ϕ8–36 bacteriophage. Named I-Bth0305I, the endonuclease cleaves a DNA target in the uninterrupted recA gene at a position immediately adjacent to the intron insertion site. The enzyme displays a multidomain, homodimeric architecture and footprints a DNA region of ∼60 bp. Its highest specificity corresponds to a 14-bp pseudopalindromic sequence that is directly centered across the DNA cleavage site. Unlike many homing endonucleases, the specificity profile of the enzyme is evenly distributed across much of its target site, such that few single base pair substitutions cause a significant decrease in cleavage activity. A crystal structure of its C-terminal domain confirms a nuclease fold that is homologous to very short patch repair (Vsr) endonucleases. The domain architecture and DNA recognition profile displayed by I-Bth0305I, which is the prototype of a homing lineage that we term the ‘EDxHD’ family, are distinct from previously characterized homing endonucleases

Mobile DNA elements in T4 and related phages

Mobile genetic elements are common inhabitants of virtually every genome where they can exert profound influences on genome structure and function in addition to promoting their own spread within and between genomes. Phage T4 and related phage have long served as a model system for understanding the molecular mechanisms by which a certain class of mobile DNA, homing endonucleases, promote their spread. Homing endonucleases are site-specific DNA endonucleases that initiate mobility by introducing double-strand breaks at defined positions in genomes lacking the endonuclease gene, stimulating repair and recombination pathways that mobilize the endonuclease coding region. In phage T4, homing endonucleases were first discovered as encoded within the self-splicing td, nrdB and nrdD introns of T4. Genomic data has revealed that homing endonucleases are extremely widespread in T-even-like phage, as evidenced by the astounding fact that ~11% of the T4 genome encodes homing endonuclease genes, with most of them located outside of self-splicing introns. Detailed studies of the mobile td intron and its encoded endonuclease, I-TevI, have laid the foundation for genetic, biochemical and structural aspects that regulate the mobility process, and more recently have provided insights into regulation of homing endonuclease function. Here, we summarize the current state of knowledge regarding T4-encoded homing endonucleases, with particular emphasis on the td/I-TevI model system. We also discuss recent progress in the biology of free-standing endonucleases, and present areas of future research for this fascinating class of mobile genetic elements

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

The Red Sea, Coastal Landscapes, and Hominin Dispersals

This chapter provides a critical assessment of environment, landscape and resources in the Red Sea region over the past five million years in relation to archaeological evidence of hominin settlement, and of current hypotheses about the role of the region as a pathway or obstacle to population dispersals between Africa and Asia and the possible significance of coastal colonization. The discussion assesses the impact of factors such as topography and the distribution of resources on land and on the seacoast, taking account of geographical variation and changes in geology, sea levels and palaeoclimate. The merits of northern and southern routes of movement at either end of the Red Sea are compared. All the evidence indicates that there has been no land connection at the southern end since the beginning of the Pliocene period, but that short sea crossings would have been possible at lowest sea-level stands with little or no technical aids. More important than the possibilities of crossing the southern channel is the nature of the resources available in the adjacent coastal zones. There were many climatic episodes wetter than today, and during these periods water draining from the Arabian escarpment provided productive conditions for large mammals and human populations in coastal regions and eastwards into the desert. During drier episodes the coastal region would have provided important refugia both in upland areas and on the emerged shelves exposed by lowered sea level, especially in the southern sector and on both sides of the Red Sea. Marine resources may have offered an added advantage in coastal areas, but evidence for their exploitation is very limited, and their role has been over-exaggerated in hypotheses of coastal colonization