Optical excitations of a self assembled artificial ion

By use of magneto-photoluminescence spectroscopy we demonstrate bias controlled single-electron charging of a single quantum dot. Neutral, single, and double charged excitons are identified in the optical spectra. At high magnetic fields one Zeeman component of the single charged exciton is found to be quenched, which is attributed to the competing effects of tunneling and spin-flip processes. Our experimental data are in good agreement with theoretical model calculations for situations where the spatial extent of the hole wave functions is smaller as compared to the electron wave functions.Comment: to be published in Physical Review B (rapid communication

Using holographic microscopy to measure the effect of confinement on crowding agents in lipid vesicles

The hydrodynamic effects of macromolecular crowding inside cells is often studied in vitro by using polymers as crowding reagents. Confinement of polymers inside cell-sized droplets has been shown to affect the diffusion of small molecules. Here we develop a method, based on digital holographic microscopy, to measure the diffusion of polystyrene microspheres that are confined within lipid vesicles containing a high concentration of solute. We apply the method to three solutes of varying complexity: sucrose, dextran, and PEG, prepared at ~7 % (w/w). We find that diffusion inside and outside the vesicles is the same when the solute is sucrose or dextran that is prepared below the critical overlap concentration. For polyethylene glycol, which is present at a concentration higher than the critical overlap concentration, the diffusion of microspheres inside vesicles is slower, hinting at the potential effects of confinement on crowding agents.Comment: 4 figures, 6 page

Neuroprotective Effects of Calmodulin Peptide 76-121aa: Disruption of Calmodulin Binding to Mutant Huntingtin

Huntington's disease (HD) is a neurodegenerative disease caused by mutant huntingtin protein containing an expanded polyglutamine tract, which may cause abnormal protein–protein interactions such as increased association with calmodulin (CaM). We previously demonstrated in HEK293 cells that a peptide containing amino acids 76-121 of CaM (CaM-peptide) interrupted the interaction between CaM and mutant huntingtin, reduced mutant huntingtin-induced cytotoxicity and reduced transglutaminase (TG)-modified mutant huntingtin. We now report that adeno-associated virus (AAV)-mediated expression of CaM-peptide in differentiated neuroblastoma SH-SY5Y cells, stably expressing an N-terminal fragment of huntingtin containing 148 glutamine repeats, significantly decreases the amount of TG-modified huntingtin and attenuates cytotoxicity. Importantly, the effect of the CaM-peptide shows selectivity, such that total TG activity is not significantly altered by expression of CaM-peptide nor is the activity of another CaM-dependent enzyme, CaM kinase II. In vitro, recombinant exon 1 of huntingtin with 44 glutamines (htt-exon1-44Q) binds to CaM-agarose; the addition of 10 µM of CaM-peptide significantly decreases the interaction of htt-exon1-44Q and CaM but not the binding between CaM and calcineurin, another CaM-binding protein. These data support the hypothesis that CaM regulates TG-catalyzed modifications of mutant huntingtin and that specific and selective disruption of the CaM-huntingtin interaction is potentially a new target for therapeutic intervention in HD

Social environment elicits lateralized navigational paths in two populations of typically developing children

The current study provides the first evidence of human lateralized navigation of a social space within a naturalistic environment. We employed a quantitative, observational approach and report on a detailed set of nearly 700 independent navigational routes from two separate child populations consisting of over 300 typically developing children, aged five to fourteen years. The navigational path was considered across the sagittal plane (left, right) around three distinct target types (peer, adult and object). Both child populations expressed a significant bias for choosing a rightward navigational path around a human tar- get (e.g. peer, adult) and no lateral preference for navigation around fixed, inanimate objects. A rightward navigational path provides an advantage for the left visual field and the right hemisphere, facilitating both the production and perception of social-emotion stimuli. The findings are consistent with evidence from studies of non-human animal species demonstrating that the social environment elicits predictable lateralized behavior, and support an early evolutionary delineation of functional processing by the two hemispheres

Cognitive Dysfunction in Huntington's Disease: Mechanisms and Therapeutic Strategies Beyond BDNF

One of the main focuses in Huntington's disease (HD) research, as well as in most of the neurodegenerative diseases, is the development of new therapeutic strategies, as currently there is no treatment to delay or prevent the progression of the disease. Neuronal dysfunction and neuronal death in HD are caused by a combination of interrelated pathogenic processes that lead to motor, cognitive and psychiatric symptoms. Understanding how mutant huntingtin impacts on a plethora of cellular functions could help to identify new molecular targets. Although HD has been classically classified as a neurodegenerative disease affecting voluntary movement, lately cognitive dysfunction is receiving increased attention as it is very invalidating for patients. Thus, an ambitious goal in HD research is to find altered molecular mechanisms that contribute to cognitive decline. In this review we have focused on those findings related to corticostriatal and hippocampal cognitive dysfunction in HD, as well as on the underlying molecular mechanisms, which constitute potential therapeutic targets. These include alterations in synaptic plasticity, transcriptional machinery, and neurotrophic and neurotransmitter signaling. This article is protected by copyright. All rights reserved

Lipid exchange promotes fusion of model protocells

Vesicle fusion is an important process underlying cell division, transport, and membrane trafficking. In phospholipid systems, a range of fusogens including divalent cations and depletants have been shown to induce adhesion, hemifusion, and then full content fusion between vesicles. This works shows that these fusogens do not perform the same function for fatty acid vesicles, which are used as model protocells (primitive cells). Even when fatty acid vesicles appear adhered or hemifused to each other, the intervening barriers between vesicles do not rupture. This difference is likely because fatty acids have a single aliphatic tail, and are more dynamic than their phospholipid counterparts. To address this, we postulate that fusion could instead occur under conditions, such as lipid exchange, that disrupt lipid packing. Using both experiments and molecular dynamics simulations, we verify that fusion in fatty acid systems can indeed be induced by lipid exchange. These results begin to probe how membrane biophysics could constrain the evolutionary dynamics of protocells.Comment: 15 pages, 7 figure

Measuring vesicle loading with holographic microscopy and bulk light scattering

We report efforts to quantify the loading of cell-sized lipid vesicles using in-line digital holographic microscopy. This method does not require fluorescent reporters, fluorescent tracers, or radioactive tracers. A single-color LED light source takes the place of conventional illumination to generate holograms rather than bright field images. By modelling the vesicle's scattering in a microscope with a Lorenz-Mie light scattering model, and comparing the results to data holograms, we are able to measure the vesicle's refractive index and thus loading. Performing the same comparison for bulk light scattering measurements enables retrieval of vesicle loading for nanoscale vesicles.Comment: 7 figure

Partial breastfeeding protects Bedouin infants from infection and morbidity: prospective cohort study

The benefits of exclusive breastfeeding for health in infants have been widely described. The goal of this study was to determine whether partial breastfeeding has protective effects against enteric infection and associated morbidity in population where early addition of supplementation is common. In this prospective study 238 Bedouin infants were followed from birth to age 18 months. Exclusive breastfeeding was protective against infection and morbidity at ages 0 to 3 months. In the age range of 4 to 6 months, partial versus non breastfeeding was associated with lower rates of infection with Cryptosporidium spp (Odds Ratio OR 0.34, 95% confidence interval CI 0.18; 0.65), and Campylobacter spp (OR 0.58, CI 0.35; 0.98), lower rates of ear infections (OR 0.47, CI 0.24; 0.90) and of asthma (OR 0.33, CI 0.13; 0.81). In older children (10-12 month age range) partial breastfeeding as compared to none, protected against infections with Cryptosporidium spp (OR 0.57, CI 0.36; 0.91) and Giardia lamblia (OR 0.92, CI 0.85; 0.99). In Bedouins, and possibly in other populations, even partial breastfeeding, especially at ages 4 to 6 months offers protection against infection. Thus, encouraging mothers to continue to at least partially breastfeed past age 3 months may help reduce infections and morbidity in infants

An analysis of bimanual actions in natural feeding of semi‐wild chimpanzees

Objective The objective of the current study was to investigate the lateral dominance for a bimanually coordinated natural feeding behavior in semi‐wild chimpanzees. Methods Strychnos spp. fruit consumption behaviors in semi‐wild chimpanzees as an ecologically comparable feeding behavior to those found in cerebral lateralization studies of non‐primate species was investigated. Video recordings of 33 chimpanzees were assessed while they consumed hard‐shelled strychnos fruits. Statistical and descriptive measures of hand dominance to highlight lateralized patterns were explored. Results Statistical evaluation of feeding bouts revealed a group‐level right‐handed bias for bimanual coordinated feeding actions, however, few individuals were statistically lateralized. Descriptive analyses revealed that the majority of individuals were lateralized and possessed a right‐handed bias for strychnos feeding behavior. Conclusions The results provided empirical evidence in support of an early evolutionary delineation of function for the right and left hemispheres. The present findings suggest that great apes express an intermediate stage along the phylogenetic trajectory of human manual lateralization