The Headgroup (A)Symmetry Strongly Determines the Aggregation Behavior of Single-Chain Phenylene-Modified Bolalipids and Their Miscibility with Classical Phospholipids

In the present work, we describe the synthesis of two single-chain phenylene-modified bolalipids, namely PC-C17pPhC17-PC and PC-C17pPhC17-OH, with either symmetrical (phosphocholine) or asymmetrical (phosphocholine and hydroxyl) headgroups using a Sonogashira cross-coupling reaction as key step. The temperature-dependent aggregation behavior of both bolalipids in aqueous suspension was studied using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, small angle neutron scattering (SANS), and X-ray scattering. We show that different headgroup symmetries lead to a change in the aggregation behavior: Whereas PC-C17pPhC17-PC forms nanofibers with a diameter of 5.7 nm that transform into small ellipsoidal micelles at 23 °C, the PC-C17pPhC17-OH self-assembles into lamellae with bolalipid molecules in an antiparallel orientation up to high temperatures. Furthermore, the mixing behavior of both bolalipids with bilayer-forming phospholipids (DPPC and DSPC) was studied by means of DSC and TEM. The aim was to stabilize bilayer membranes formed of phospholipids in order to improve these mixed lipid vesicles for drug delivery purposes. We show that the symmetrical PC-C17pPhC17-PC is miscible with DPPC and DSPC; however, closed lipid vesicles are not observed, and elongated micelles and bilayer fragments are found instead. In contrast, the asymmetrical PC-C17pPhC17-OH shows no miscibility with phospholipids at all

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

In the present work, we describe the synthesis of a single-chain, phenylene-modified bolalipid with two phosphocholine headgroups, PC-C18pPhC18-PC, using a Sonogashira cross-coupling reaction as a key step. The aggregation behaviour was studied as a function of temperature using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and small angle neutron scattering (SANS). We show that our new bolalipid self-assembles into nanofibres, which transform into flexible nanofibres at 27 °C and further to small elongated micelles at 45 °C. Furthermore, the miscibility of the bolalipid with bilayer-forming phosphatidylcholines (DMPC, DPPC, and DSPC) was investigated by means of DSC, TEM, FTIR, and small angle X-ray scattering (SAXS). We could show that the PC-C18pPhC18-PC is partially miscible with saturated phosphatidylcholines; however, closed lipid vesicles with an increased thermal stability were not found. Instead, bilayer fragments and disk-like aggregates are formed

The Vjosa River corridor: a model of natural hydro-morphodynamics and a hotspot of highly threatened ecosystems of European significance

Context: Large near-natural rivers have become rare in Europe, a fact reflected in the high conservation status of many riverine ecosystems. While the Balkan still harbors several intact river corridors, most of these are under pressure from planned hydropower constructions. Unfortunately, there is little information available on the hydromorphodynamics and biota of Balkan rivers under threat. Objectives: We present a synthesis of research on the Vjosa in Southern Albania. Here, longitudinal continuity in water flow, undisturbed sediment transport and intact fluvial dynamics are still maintained, but threatened by two large dams planned in its downstream section. We intend to provide a first multidisciplinary inventory of this river system as an example of the knowledge base required for sound water management decisions in the Balkans. Methods: Based on field work of a multidisciplinary consortium of scientists from Albania and other countries conducted from 2017 onwards, we summarize the most important findings on geomorphology of the riverine landscape, habitat turnover rates, vegetation ecology and selected animal taxa. Results: We found evidence that significant areas (86%) of the river corridor are covered by habitats listed in Annex 1 of the European Union Habitats Directive. These are associated with a high number of threatened biota. Conclusions: Our findings underscore the value of the Vjosa as one of the few remaining reference sites for dynamic floodplains in Europe and as a natural laboratory for interdisciplinary research. We emphasize that such multidisciplinary studies are a prerequisite for informed evaluation of potential impacts caused by hydropower plants

Quality Assessment and Data Analysis for microRNA Expression Arrays

MicroRNAs are small (∼22 nt) RNAs that regulate gene expression and play important roles in both normal and disease physiology. The use of microarrays for global characterization of microRNA expression is becoming increasingly popular and has the potential to be a widely used and valuable research tool. However, microarray profiling of microRNA expression raises a number of data analytic challenges that must be addressed in order to obtain reliable results. We introduce here a universal reference microRNA reagent set as well as a series of nonhuman spiked-in synthetic microRNA controls, and demonstrate their use for quality control and between-array normalization of microRNA expression data. We also introduce diagnostic plots designed to assess and compare various normalization methods. We anticipate that the reagents and analytic approach presented here will be useful for improving the reliability of microRNA microarray experiments

The health and well-being of transgender high school students: results from the New Zealand adolescent health survey (Youth’12).

Purpose To report the prevalence of students according to four gender groups (i.e., those who reported being non-transgender, transgender, or not sure about their gender, and those who did not understand the transgender question), and to describe their health and well-being. Methods Logistic regressions were used to examine the associations between gender groups and selected outcomes in a nationally representative high school health and well-being survey, undertaken in 2012. Results Of the students (n = 8,166), 94.7% reported being non-transgender, 1.2% reported being transgender, 2.5% reported being not sure about their gender, and 1.7% did not understand the question. Students who reported being transgender or not sure about their gender or did not understand the question had compromised health and well-being relative to their nontransgender peers; in particular, for transgender students perceiving that a parent cared about them (odds ratio [OR], .3; 95% confidence interval[CI], .2 -.4), depressive symptoms (OR, 5.7; 95% CI, 3.6-9.2), suicide attempts (OR, 5.0; 95% CI, 2.9-8.8), and school bullying (OR, 4.5; 95% CI, 2.4-8.2). Conclusions This is the first nationally representative survey to report the health and well-being of students who report being transgender. We found that transgender students and those reporting not being sure are a numerically small but important group. Transgender students are diverse and are represented across demographic variables, including their sexual attractions. Transgender youth face considerable health and well-being disparities. It is important to address the challenging environments these students face and to increase access to responsive services for transgender youth

Inherent High Correlation of Individual Motility Enhances Population Dispersal in a Heterotrophic, Planktonic Protist

Quantitative linkages between individual organism movements and the resulting population distributions are fundamental to understanding a wide range of ecological processes, including rates of reproduction, consumption, and mortality, as well as the spread of diseases and invasions. Typically, quantitative data are collected on either movement behaviors or population distributions, rarely both. This study combines empirical observations and model simulations to gain a mechanistic understanding and predictive ability of the linkages between both individual movement behaviors and population distributions of a single-celled planktonic herbivore. In the laboratory, microscopic 3D movements and macroscopic population distributions were simultaneously quantified in a 1L tank, using automated video- and image-analysis routines. The vertical velocity component of cell movements was extracted from the empirical data and used to motivate a series of correlated random walk models that predicted population distributions. Validation of the model predictions with empirical data was essential to distinguish amongst a number of theoretically plausible model formulations. All model predictions captured the essence of the population redistribution (mean upward drift) but only models assuming long correlation times (minute), captured the variance in population distribution. Models assuming correlation times of 8 minutes predicted the least deviation from the empirical observations. Autocorrelation analysis of the empirical data failed to identify a de-correlation time in the up to 30-second-long swimming trajectories. These minute-scale estimates are considerably greater than previous estimates of second-scale correlation times. Considerable cell-to-cell variation and behavioral heterogeneity were critical to these results. Strongly correlated random walkers were predicted to have significantly greater dispersal distances and more rapid encounters with remote targets (e.g. resource patches, predators) than weakly correlated random walkers. The tendency to disperse rapidly in the absence of aggregative stimuli has important ramifications for the ecology and biogeography of planktonic organisms that perform this kind of random walk

Modeling Activity and Target-Dependent Developmental Cell Death of Mouse Retinal Ganglion Cells Ex Vivo

Programmed cell death is widespread during the development of the central nervous system and serves multiple purposes including the establishment of neural connections. In the mouse retina a substantial reduction of retinal ganglion cells (RGCs) occurs during the first postnatal week, coinciding with the formation of retinotopic maps in the superior colliculus (SC). We previously established a retino-collicular culture preparation which recapitulates the progressive topographic ordering of RGC projections during early post-natal life. Here, we questioned whether this model could also be suitable to examine the mechanisms underlying developmental cell death of RGCs. Brn3a was used as a marker of the RGCs. A developmental decline in the number of Brn3a-immunolabelled neurons was found in the retinal explant with a timing that paralleled that observed in vivo. In contrast, the density of photoreceptors or of starburst amacrine cells increased, mimicking the evolution of these cell populations in vivo. Blockade of neural activity with tetrodotoxin increased the number of surviving Brn3a-labelled neurons in the retinal explant, as did the increase in target availability when one retinal explant was confronted with 2 or 4 collicular slices. Thus, this ex vivo model reproduces the developmental reduction of RGCs and recapitulates its regulation by neural activity and target availability. It therefore offers a simple way to analyze developmental cell death in this classic system. Using this model, we show that ephrin-A signaling does not participate to the regulation of the Brn3a population size in the retina, indicating that eprhin-A-mediated elimination of exuberant projections does not involve developmental cell death