Saccharomyces cerevisiae mutants affected in vacuole assembly or vacuolar H+-ATPase are hypersensitive to lead (Pb) toxicity

Lead is an important environmental pollutant. The role of vacuole, in Pb detoxification, was studied using a vacuolar protein sorting mutant strain (vps16Δ), belonging to class C mutants. Cells disrupted in VPS16 gene, did not display a detectable vacuolar-like structure. Based on the loss of cell proliferation capacity, it was found that cells from vps16Δ mutant exhibited a hypersensitivity to Pb-induced toxicity, compared to wild type (WT) strain. The function of vacuolar H+-ATPase (V-ATPase), in Pb detoxification, was evaluated using mutants with structurally normal vacuoles but defective in subunits of catalytic (vma1Δ or vma2Δ) or membrane domain (vph1Δ or vma3Δ) of V-ATPase. All mutants tested, lacking a functional V-ATPase, displayed an increased susceptibility to Pb, comparatively to cells from WT strain. Modification of vacuolar morphology, in Pb-exposed cells, was visualized using a Vma2p-GFP strain. The treatment of yeast cells with Pb originated the fusion of the medium size vacuolar lobes into one enlarged vacuole. In conclusion, it was found that vacuole plays an important role in the detoxification of Pb in Saccharomyces cerevisiae; in addition, a functional V-ATPase was required for Pb compartmentalization.The authors thank the Fundacao para a Ciencia e a Tecnologia (FCT) through the Portuguese Government for their financial support of this work through the grant PEST-OE/EQB/LA0023/2011 to IBB

Mouse Gestation Length Is Genetically Determined

Background: Preterm birth is an enormous public health problem, affecting over 12 % of live births and costing over $26 billion in the United States alone. The causes are complex, but twin studies support the role of genetics in determining gestation length. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that actually address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined. Methodology/Principal Findings: To further develop the mouse as a genetic model of preterm birth, we developed a highthroughput monitoring system and measured the gestation length in 15 inbred strains. Our results show an unexpectedly wide variation in overall gestation length between strains that approaches two full days, while intra-strain variation is quite low. Although litter size shows a strong inverse correlation with gestation length, genetic difference alone accounts for a significant portion of the variation. In addition, ovarian transplant experiments support a primary role of maternal genetics in the determination of gestation length. Preliminary analysis of gestation length in the C57BL/6J-Chr # A/J /NaJ chromosome substitution strain (B.A CSS) panel suggests complex genetic control of gestation length. Conclusions/Significance: Together, these data support the role of genetics in regulating gestation length and present th

Determination of Vitamin A and its Metabolites in Rat Testis: Possible Involvement of Vitamin A in Testicular Toxicity Caused by Molinate

This study was conducted to evaluate the effect of molinate on retinoids homeostasis in rat testis. Molinate was administrated to male Sprague–Dawley rats (200 mg kg−1 in corn oil, ip). Retinoid measurements were made at 6, 12, 48 and 168 h time points after administration. Testis levels of retinoic acid decreased (32 %) in a statistically significant manner at the 12 and 48 h time points. However, retinol and retinaldehyde were not significantly affected by molinate. These results suggest that molinate affects retinoic acid synthesis in testis and could contribute to understanding the molecular mechanism of molinate involved testicular toxicity

Predictors of patient satisfaction with hospital health care

BACKGROUND: We used a validated inpatient satisfaction questionnaire to evaluate the health care received by patients admitted to several hospitals. This questionnaire was factored into distinct domains, creating a score for each to assist in the analysis. We evaluated possible predictors of patient satisfaction in relation to socio-demographic variables, history of admission, and survey logistics. METHODS: Cross-sectional study of patients discharged from four acute care general hospitals. Random sample of 650 discharged patients from the medical and surgical wards of each hospital during February and March 2002. A total of 1,910 patients responded to the questionnaire (73.5%). Patient satisfaction was measured by a validated questionnaire with six domains: information, human care, comfort, visiting, intimacy, and cleanliness. Each domain was scored from 0 to 100, with higher scores indicating higher levels of patient satisfaction. RESULTS: In the univariate analysis, age was related to all domains except visiting; gender to comfort, visiting, and intimacy; level of education to comfort and cleanliness; marital status to information, human care, intimacy, and cleanliness; length of hospital stay to visiting and cleanliness, and previous admissions to human care, comfort, and cleanliness. The timing of the response to the mailing and who completed the questionnaire were related to all variables except visiting and cleanliness. Multivariate analysis confirmed in most cases the previous findings and added additional correlations for level of education (visiting and intimacy) and marital status (comfort and visiting). CONCLUSION: These results confirm the varying importance of some socio-demographic variables and length of stay, previous admission, the timing of response to the questionnaire, and who completed the questionnaire on some aspects of patient satisfaction after hospitalization. All these variables should be considered when evaluating patient satisfaction

Observation of a phononic quadrupole topological insulator

The modern theory of charge polarization in solids is based on a generalization of Berry’s phase. The possibility of the quantization of this phase arising from parallel transport in momentum space is essential to our understanding of systems with topological band structures. Although based on the concept of charge polarization, this same theory can also be used to characterize the Bloch bands of neutral bosonic systems such as photonic or phononic crystals. The theory of this quantized polarization has recently been extended from the dipole moment to higher multipole moments. In particular, a two-dimensional quantized quadrupole insulator is predicted to have gapped yet topological one-dimensional edge modes, which stabilize zero-dimensional in-gap corner states. However, such a state of matter has not previously been observed experimentally. Here we report measurements of a phononic quadrupole topological insulator. We experimentally characterize the bulk, edge and corner physics of a mechanical metamaterial (a material with tailored mechanical properties) and find the predicted gapped edge and in-gap corner states. We corroborate our findings by comparing the mechanical properties of a topologically non-trivial system to samples in other phases that are predicted by the quadrupole theory. These topological corner states are an important stepping stone to the experimental realization of topologically protected wave guides in higher dimensions, and thereby open up a new path for the design of metamaterials

Probe-caught spontaneous and deliberate mind wandering in relation to self-reported inattentive, hyperactive and impulsive traits in adults.

Research has revealed a positive relationship between types of mind wandering and ADHD at clinical and subclinical levels. However, this work did not consider the relationship between mind wandering and the core symptoms of ADHD: inattention, hyperactivity and impulsivity. Given that the DMS-V attributes mind wandering to inattention only, and that only inattention is thought to result from impairment to the executive function linked to mind wandering, the present research sought to examine this relationship in 80 undiagnosed adults. Using both standard and easy versions of the Sustained Attention to Response Task (SART) we measured both spontaneous and deliberate mind wandering. We found that spontaneous mind wandering was related to self-reported inattentive traits when the task was cognitively more challenging (standard SART). However, hyperactive and impulsive traits were related to spontaneous mind wandering independent of task difficulty. The results suggest inattentive traits are not uniquely related to mind wandering; indeed, adults with hyperactive/impulsive traits were more likely to experience mind wandering, suggesting that mind wandering might not be useful diagnostic criteria for inattention

Should young people be paid for getting tested? A national comparative study to evaluate patient financial incentives for chlamydia screening

<p>Abstract</p> <p>Background</p> <p>Patient financial incentives ("incentives") have been widely used to promote chlamydia screening uptake amongst 15-24 year olds in England, but there is scarce evidence of their effectiveness. The objectives of the study were to describe incentives used to promote chlamydia screening in Primary Care Trusts (PCTs) in England and to evaluate their impact on coverage and positivity rate.</p> <p>Methods</p> <p>PCTs that had used incentives between 1/1/2007 and 30/6/2009 (exposed) were matched by socio-demographic profile and initial screening coverage with PCTs that had not (unexposed). For each PCT, percentage point change in chlamydia screening coverage and positivity for the period before and during the incentive was calculated. Differences in average change of coverage and positivity rate between exposed and unexposed PCTs were compared using linear regression to adjust for matching and potential confounders.</p> <p>Results</p> <p>Incentives had a significant effect in increasing average coverage in exposed PCTs (0.43%, CI 0.04%-0.82%). The effect for voucher schemes (2.35%) was larger than for prize draws (0.16%). The difference was greater in females (0.73%) than males (0.14%). The effect on positivity rates was not significant (0.07%, CI -1.53% to 1.67%).</p> <p>Conclusions</p> <p>Vouchers, but not prize draws, led to a small absolute but large relative increase in chlamydia screening coverage. Incentives increased coverage more in females than males but had no impact on reported positivity rates. These findings support recommendations not to use prize draws to promote chlamydia screening and contribute to the evidence base of the operational effectiveness of using patient incentives in encouraging public health action.</p

Retinol Metabolism in the Mollusk Osilinus lineatus Indicates an Ancient Origin for Retinyl Ester Storage Capacity

Although retinoids have been reported to be present and active in vertebrates and invertebrates, the presence of mechanisms for retinoid storage in the form of retinyl esters, a key feature to maintain whole-organism retinoid homeostasis, have been considered to date a vertebrate innovation. Here we demonstrate for the first time the presence of retinol and retinyl esters in an invertebrate lophotrochozoan species, the gastropod mollusk Osilinus lineatus. Furthermore, through a pharmacological approach consisting of intramuscular injections of different retinoid precursors, we also demonstrate that the retinol esterification pathway is active in vivo in this species. Interestingly, retinol and retinyl esters were only detected in males, suggesting a gender-specific role for these compounds in the testis. Females, although lacking detectable levels of retinol or retinyl esters, also have the biochemical capacity to esterify retinol, but at a lower rate than males. The occurrence of retinyl ester storage capacity, together with the presence in males and females of active retinoids, i.e., retinoic acid isomers, indicates that O. lineatus has a well developed retinoid system. Hence, the present data strongly suggest that the capacity to maintain retinoid homeostasis has arisen earlier in Bilateria evolution than previously thought

Accumulation of an Antidepressant in Vesiculogenic Membranes of Yeast Cells Triggers Autophagy

Many antidepressants are cationic amphipaths, which spontaneously accumulate in natural or reconstituted membranes in the absence of their specific protein targets. However, the clinical relevance of cellular membrane accumulation by antidepressants in the human brain is unknown and hotly debated. Here we take a novel, evolutionarily informed approach to studying the effects of the selective-serotonin reuptake inhibitor sertraline/Zoloft® on cell physiology in the model eukaryote Saccharomyces cerevisiae (budding yeast), which lacks a serotonin transporter entirely. We biochemically and pharmacologically characterized cellular uptake and subcellular distribution of radiolabeled sertraline, and in parallel performed a quantitative ultrastructural analysis of organellar membrane homeostasis in untreated vs. sertraline-treated cells. These experiments have revealed that sertraline enters yeast cells and then reshapes vesiculogenic membranes by a complex process. Internalization of the neutral species proceeds by simple diffusion, is accelerated by proton motive forces generated by the vacuolar H+-ATPase, but is counteracted by energy-dependent xenobiotic efflux pumps. At equilibrium, a small fraction (10–15%) of reprotonated sertraline is soluble while the bulk (90–85%) partitions into organellar membranes by adsorption to interfacial anionic sites or by intercalation into the hydrophobic phase of the bilayer. Asymmetric accumulation of sertraline in vesiculogenic membranes leads to local membrane curvature stresses that trigger an adaptive autophagic response. In mutants with altered clathrin function, this adaptive response is associated with increased lipid droplet formation. Our data not only support the notion of a serotonin transporter-independent component of antidepressant function, but also enable a conceptual framework for characterizing the physiological states associated with chronic but not acute antidepressant administration in a model eukaryote

A protease-based biosensor for the detection of schistosome cercariae

Parasitic diseases affect millions of people worldwide, causing debilitating illnesses and death. Rapid and cost-effective approaches to detect parasites are needed, especially in resource-limited settings. A common signature of parasitic diseases is the release of specific proteases by the parasites at multiple stages during their life cycles. To this end, we engineered several modular Escherichia coli and Bacillus subtilis whole-cell-based biosensors which incorporate an interchangeable protease recognition motif into their designs. Herein, we describe how several of our engineered biosensors have been applied to detect the presence and activity of elastase, an enzyme released by the cercarial larvae stage of Schistosoma mansoni. Collectively, S. mansoni and several other schistosomes are responsible for the infection of an estimated 200 million people worldwide. Since our biosensors are maintained in lyophilised cells, they could be applied for the detection of S. mansoni and other parasites in settings without reliable cold chain access