Selected tools to visualize membrane interactions

In the past decade, we developed various fluorescence-based methods for monitoring membrane fusion, membrane docking, distances between membranes, and membrane curvature. These tools were mainly developed using liposomes as model systems, which allows for the dissection of specific interactions mediated by, for example, fusion proteins. Here, we provide an overview of these methods, including two-photon fluorescence cross-correlation spectroscopy and intramembrane Förster energy transfer, with asymmetric labelling of inner and outer membrane leaflets and the calibrated use of transmembrane energy transfer to determine membrane distances below 10 nm. We discuss their application range and their limitations using examples from our work on protein-mediated vesicle docking and fusion

Relationship between a Weighted Multi-Gene Algorithm and Blood Pressure Control in Hypertension

Hypertension (HTN) is a complex disease with interactions among multiple organ systems, including the heart, vasculature, and kidney with a strong heritable component. Despite the multifactorial nature of HTN, no clinical guidelines utilize a multi-gene approach to guide blood pressure (BP) therapy. Non-smokers with a family history of HTN were included in the analysis (n = 384; age = 61.0 ± 0.9, 11% non-white). A total of 17 functional genotypes were weighted according to the previous effect size in the literature and entered into an algorithm. Pharmacotherapy was ranked from 1⁻4 as most to least likely to respond based on the algorithmic assessment of individual patient's genotypes. Three-years of data were assessed at six-month intervals for BP and medication history. There was no difference in BP at diagnosis between groups matching the top drug recommendation using the multi-gene weighted algorithm (n = 92) vs. those who did not match (n = 292). However, from diagnosis to nadir, patients who matched the primary recommendation had a significantly greater drop in BP when compared to patients who did not. Further, the difference between diagnosis to current 1-year average BP was lower in the group that matched the top recommendation. These data suggest an association between a weighted multi-gene algorithm on the BP response to pharmacotherapy.Geneticure Inc.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Risk-shifting Through Issuer Liability and Corporate Monitoring

This article explores how issuer liability re-allocates fraud risk and how risk allocation may reduce the incidence of fraud. In the US, the apparent absence of individual liability of officeholders and insufficient monitoring by insurers under-mine the potential deterrent effect of securities litigation. The underlying reasons why both mechanisms remain ineffective are collective action problems under the prevailing dispersed ownership structure, which eliminates the incentives to moni-tor set by issuer liability. This article suggests that issuer liability could potentially have a stronger deterrent effect when it shifts risk to individuals or entities holding a larger financial stake. Thus, it would enlist large shareholders in monitoring in much of Europe. The same risk-shifting effect also has implications for the debate about the relationship between securities litigation and creditor interests. Credi-tors’ claims should not be given precedence over claims of defrauded investors (e.g., because of the capital maintenance principle), since bearing some of the fraud risk will more strongly incentivise large creditors, such as banks, to monitor the firm in jurisdictions where corporate debt is relatively concentrated

Ketogenic diet as a glycine lowering therapy in nonketotic hyperglycinemia and impact on brain glycine levels

BACKGROUND: Nonketotic hyperglycinemia (NKH) is a severe neurometabolic disorder characterized by increased glycine levels. Current glycine reduction therapy uses high doses of sodium benzoate. The ketogenic diet (KD) may represent an alternative method of glycine reduction. AIM: We aimed to assess clinical and biochemical effects of two glycine reduction strategies: high dose benzoate versus KD with low dose benzoate. METHODS: Six infants with NKH were first treated with high dose benzoate therapy to achieve target plasma glycine levels, and then switched to KD with low dose benzoate. They were evaluated as clinically indicated by physical examination, electroencephalogram, plasma and cerebral spinal fluid amino acid levels. Brain glycine levels were monitored by magnetic resonance spectroscopy (MRS). RESULTS: Average plasma glycine levels were significantly lower with KD compared to benzoate monotherapy by on average 28%. Two infants underwent comparative assessments of brain glycine levels via serial MRS. A 30% reduction of brain glycine levels was observed in the basal ganglia and a 50% reduction in the white matter, which remained elevated above normal, and was equivalent between the KD and high dose benzoate therapies. CSF analysis obtained while participants remained on the KD showed a decrease in glycine, serine and threonine levels, reflecting their gluconeogenetic usage. Clinically, half the patients had seizure reduction on KD, otherwise the clinical impact was variable. CONCLUSION: KD is an effective glycine reduction method in NKH, and may provide a more consistent reduction in plasma glycine levels than high-dose benzoate therapy. Both high-dose benzoate therapy and KD equally reduced but did not normalize brain glycine levels even in the setting of low-normal plasma glycine

Spitzer Follow-up of Extremely Cold Brown Dwarfs Discovered by the Backyard Worlds: Planet 9 Citizen Science Project

We present Spitzer follow-up imaging of 95 candidate extremely cold brown dwarfs discovered by the Backyard Worlds: Planet 9 citizen science project, which uses visually perceived motion in multiepoch Wide-field Infrared Survey Explorer (WISE) images to identify previously unrecognized substellar neighbors to the Sun. We measure Spitzer [3.6]–[4.5] color to phototype our brown dwarf candidates, with an emphasis on pinpointing the coldest and closest Y dwarfs within our sample. The combination of WISE and Spitzer astrometry provides quantitative confirmation of the transverse motion of 75 of our discoveries. Nine of our motion-confirmed objects have best-fit linear motions larger than 1'' yr⁻¹; our fastest-moving discovery is WISEA J155349.96+693355.2 (μ ≈ 2.”15 yr⁻¹), a possible T-type subdwarf. We also report a newly discovered wide-separation (~400 au) T8 comoving companion to the white dwarf LSPM J0055+5948 (the fourth such system to be found), plus a candidate late T companion to the white dwarf LSR J0002+6357 at 5 5 projected separation (~8700 au if associated). Among our motion-confirmed targets, five have Spitzer colors most consistent with spectral type Y. Four of these five have exceptionally red Spitzer colors suggesting types of Y1 or later, adding considerably to the small sample of known objects in this especially valuable low-temperature regime. Our Y dwarf candidates begin bridging the gap between the bulk of the Y dwarf population and the coldest known brown dwarf

Spitzer Follow-up of Extremely Cold Brown Dwarfs Discovered by the Backyard Worlds: Planet 9 Citizen Science Project

We present Spitzer follow-up imaging of 95 candidate extremely cold brown dwarfs discovered by the Backyard Worlds: Planet 9 citizen science project, which uses visually perceived motion in multi-epoch WISE images to identify previously unrecognized substellar neighbors to the Sun. We measure Spitzer [3.6]-[4.5] color to phototype our brown dwarf candidates, with an emphasis on pinpointing the coldest and closest Y dwarfs within our sample. The combination of WISE and Spitzer astrometry provides quantitative confirmation of the transverse motion of 75 of our discoveries. Nine of our motion-confirmed objects have best-fit linear motions larger than 1"/yr; our fastest-moving discovery is WISEA J155349.96+693355.2 (total motion ~2.15"/yr), a possible T type subdwarf. We also report a newly discovered wide-separation (~400 AU) T8 comoving companion to the white dwarf LSPM J0055+5948 (the fourth such system to be found), plus a candidate late T companion to the white dwarf LSR J0002+6357 at 5.5' projected separation (~8,700 AU if associated). Among our motion-confirmed targets, five have Spitzer colors most consistent with spectral type Y. Four of these five have exceptionally red Spitzer colors suggesting types of Y1 or later, adding considerably to the small sample of known objects in this especially valuable low-temperature regime. Our Y dwarf candidates begin bridging the gap between the bulk of the Y dwarf population and the coldest known brown dwarf.Comment: accepted for publication in The Astrophysical Journa

Effects of aversive odour presentation on inhibitory control in the Stroop colour-word interference task

<p>Abstract</p> <p>Background</p> <p>Due to the unique neural projections of the olfactory system, odours have the ability to directly influence affective processes. Furthermore, it has been shown that emotional states can influence various non-emotional cognitive tasks, such as memory and planning. However, the link between emotional and cognitive processes is still not fully understood. The present study used the olfactory pathway to induce a negative emotional state in humans to investigate its effect on inhibitory control performance in a standard, single-trial manual Stroop colour-word interference task. An unpleasant (H₂S) and an emotionally neutral (Eugenol) odorant were presented in two separate experimental runs, both in blocks alternating with ambient air, to 25 healthy volunteers, while they performed the cognitive task.</p> <p>Results</p> <p>Presentation of the unpleasant odorant reduced Stroop interference by reducing the reaction times for incongruent stimuli, while the presentation of the neutral odorant had no effect on task performance.</p> <p>Conclusions</p> <p>The odour-induced negative emotional state appears to facilitate cognitive processing in the task used in the present study, possibly by increasing the amount of cognitive control that is being exerted. This stands in contrast to other findings that showed impaired cognitive performance under odour-induced negative emotional states, but is consistent with models of mood-congruent processing.</p

Ultrafast transient absorption spectroscopy: principles and application to photosynthetic systems

The photophysical and photochemical reactions, after light absorption by a photosynthetic pigment–protein complex, are among the fastest events in biology, taking place on timescales ranging from tens of femtoseconds to a few nanoseconds. The advent of ultrafast laser systems that produce pulses with femtosecond duration opened up a new area of research and enabled investigation of these photophysical and photochemical reactions in real time. Here, we provide a basic description of the ultrafast transient absorption technique, the laser and wavelength-conversion equipment, the transient absorption setup, and the collection of transient absorption data. Recent applications of ultrafast transient absorption spectroscopy on systems with increasing degree of complexity, from biomimetic light-harvesting systems to natural light-harvesting antennas, are presented. In particular, we will discuss, in this educational review, how a molecular understanding of the light-harvesting and photoprotective functions of carotenoids in photosynthesis is accomplished through the application of ultrafast transient absorption spectroscopy