Formation of PbSe/CdSe Core/Shell Nanocrystals for Stable Near-Infrared High Photoluminescence Emission

PbSe/CdSe core/shell nanocrystals with quantum yield of 70% were obtained by the “successive ion layer adsorption and reaction” technology in solution. The thickness of the CdSe shell was exactly controlled. A series of spectral red shifts with the CdSe shell growth were observed, which was attributed to the combined effect of the surface polarization and the expansion of carriers’ wavefunctions. The stability of PbSe nanocrystals was tremendously improved with CdSe shells

Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABAA receptor positive allosteric modulator

Zuranolone (SAGE-217) is a novel, synthetic, clinical stage neuroactive steroid GABAA receptor positive allosteric modulator designed with the pharmacokinetic properties to support oral daily dosing. In vitro, zuranolone enhanced GABAA receptor current at nine unique human recombinant receptor subtypes, including representative receptors for both synaptic (γ subunit-containing) and extrasynaptic (δ subunit-containing) configurations. At a representative synaptic subunit configuration, α1β2γ2, zuranolone potentiated GABA currents synergistically with the benzodiazepine diazepam, consistent with the non-competitive activity and distinct binding sites of the two classes of compounds at synaptic receptors. In a brain slice preparation, zuranolone produced a sustained increase in GABA currents consistent with metabotropic trafficking of GABAA receptors to the cell surface. In vivo, zuranolone exhibited potent activity, indicating its ability to modulate GABAA receptors in the central nervous system after oral dosing by protecting against chemo-convulsant seizures in a mouse model and enhancing electroencephalogram β-frequency power in rats. Together, these data establish zuranolone as a potent and efficacious neuroactive steroid GABAA receptor positive allosteric modulator with drug-like properties and CNS exposure in preclinical models. Recent clinical data support the therapeutic promise of neuroactive steroid GABAA receptor positive modulators for treating mood disorders; brexanolone is the first therapeutic approved specifically for the treatment of postpartum depression. Zuranolone is currently under clinical investigation for the treatment of major depressive episodes in major depressive disorder, postpartum depression, and bipolar depression

Combined Anterior-Posterior Surgery Versus Posterior Surgery for Thoracolumbar Burst Fractures: A Systematic Review of the Literature

Abstract: Study Design: A systematic quantitative review of the literature. Objective: To compare combined anterior-posterior surgery versus posterior surgery for thoracolumbar fractures in order to identify better treatments. Summary of Background Data: Axial load of the anterior and middle column of the spine can lead to a burst fracture in the vertebral body. The management of thoracolumbar burst fractures remains controversial. The goals of operative treatment are fracture reduction, fixation and decompressing the neural canal. For this, different operative methods are developed, for instance, the posterior and the combined anterior-posterior approach. Recent systematic qualitative reviews comparing these methods are lacking. Methods: We conducted an electronic search of MEDLINE, EMBASE, LILACS and the Cochrane Central Register for Controlled Trials. Results: Five observational comparative studies and no randomized clinical trials comparing the combined anteriorposterior approach with the posterior approach were retrieved. The total enrollment of patients in these studies was 755 patients. The results were expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes with 95% confidence intervals (CI). Conclusions: A small significantly higher kyphotic correction and improvement of vertebral height (sagittal index) observed for the combined anterior-posterior group is cancelled out by more blood loss, longer operation time, longer hospital stay, higher costs and a possible higher intra- and postoperative complication rate requiring re-operation and the possibility of a worsened Hannover spine score. The surgeons’ choices regarding the operative approach are biased: worse cases tended to undergo the combined anterior-posterior approach

Natural variation in immune responses to neonatal mycobacterium bovis bacillus calmette-guerin (BCG) vaccination in a cohort of Gambian infants

Background There is a need for new vaccines for tuberculosis (TB) that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-) is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN- responses to BCG in this age group are poorly described. Characterisation of IFN- responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. Methodology/Principal Findings 236 healthy Gambian babies were vaccinated with M. bovis BCG at birth. IFN-, interleukin (IL)-5 and IL-13 responses to purified protein derivative (PPD), killed Mycobacterium tuberculosis (KMTB), M. tuberculosis short term culture filtrate (STCF) and M. bovis BCG antigen 85 complex (Ag85) were measured in a whole blood assay two months after vaccination. Cytokine responses varied up to 10 log-fold within this population. The majority of infants (89-98% depending on the antigen) made IFN- responses and there was significant correlation between IFN- responses to the different mycobacterial antigens (Spearman’s coefficient ranged from 0.340 to 0.675, p=10-6-10-22). IL-13 and IL-5 responses were generally low and there were more non-responders (33-75%) for these cytokines. Nonetheless, significant correlations were observed for IL-13 and IL-5 responses to different mycobacterial antigens Conclusions/Significance Cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine variation in IFN- responses

Smoothing a rugged protein folding landscape by sequence-based redesign

The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as $\alpha_1$-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create $\textit{conserpin}$, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics.BTP is a Medical Research Council Career Development Fellow. AAN and JJH are supported by the Wellcome Trust (grant number WT 095195). SM acknowledges fellowship support from the Australian Research Council (FT100100960). NAB is an Australian Research Council Future Fellow (110100223). GIW is an Australian Research Council Discovery Outstanding Researcher Award Fellow (DP140100087). AMB is a National Health and Medical Research Senior Research Fellow (1022688). JCW is an NHMRC Senior Principal Research fellow and also acknowledges the support of an ARC Federation Fellowship. We thank the Australian Synchrotron for beam-time and technical assistance. This work was supported by the Multi-modal Australian ScienceS Imaging and Visualisation Environment (MASSIVE) (www.massive.org.au). We acknowledge the Monash Protein Production Unit and Monash Macromolecular Crystallization Facilit

Smoothing a rugged protein folding landscape by sequence-based redesign

The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as α1-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics

Three-Dimensional Manganese Oxide@Carbon Networks as Free-Standing, High-Loading Cathodes for High-Performance Zinc-Ion Batteries

Zinc-ion batteries (ZIBs), which are inexpensive and environmentally friendly, have a lot of potential for use in grid-scale energy storage systems, but their use is constrained by the availability of suitable cathode materials. MnO2-based cathodes are emerging as a promising contenders, due to the great availability and safety, as well as the device's stable output voltage platform (1.5 V). Improving the slow kinetics of MnO2-based cathodes caused by low electrical conductivity and mass diffusion rate is a challenge for their future use in next-generation rapid charging devices. Herein, the aforementioned challenges are overcome by proposing a sodium-intercalated manganese oxide (NMO) with 3D varying thinness carbon nanotubes (VTCNTs) networks as appropriate free-standing, binder-free cathodes (NMO/VTCNTs) without any heat treatment. A network construction strategy based on CNTs of different diameters is proposed for the first time to provide high specific capacity while achieving high mass loading. The specific capacity of as-prepared cathodes is significantly increased. The resulting free-standing binder-free cathodes achieve excellent capacity (329 mAh g−1 after 120 cycles at 0.2 A g−1 and 225 mAh g−1 after 200 cycles at 1 A g−1) and long-term cycling stability (158 mAh g−1 at 2 A g−1 after 1000 cycles)

Star forming dwarf galaxies

Star forming dwarf galaxies (SFDGs) have a high gas content and low metallicities, reminiscent of the basic entities in hierarchical galaxy formation scenarios. In the young universe they probably also played a major role in the cosmic reionization. Their abundant presence in the local volume and their youthful character make them ideal objects for detailed studies of the initial stellar mass function (IMF), fundamental star formation processes and its feedback to the interstellar medium. Occasionally we witness SFDGs involved in extreme starbursts, giving rise to strongly elevated production of super star clusters and global superwinds, mechanisms yet to be explored in more detail. SFDGs is the initial state of all dwarf galaxies and the relation to the environment provides us with a key to how different types of dwarf galaxies are emerging. In this review we will put the emphasis on the exotic starburst phase, as it seems less important for present day galaxy evolution but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres