Human Epidermal Neural Crest Stem Cells (hEPI-NCSC)—Characterization and Directed Differentiation into Osteocytes and Melanocytes

Here we describe the isolation, characterisation and ex-vivo expansion of human epidermal neural crest stem cells (hEPI-NCSC) and we provide protocols for their directed differentiation into osteocytes and melanocytes. hEPI-NCSC are neural crest-derived multipotent stem cells that persist into adulthood in the bulge of hair follicles. Multipotency and self-renewal were determined by in vitro clonal analyses. hEPI-NCSC generate all major neural crest derivatives, including bone/cartilage cells, neurons, Schwann cells, myofibroblasts and melanocytes. Furthermore, hEPI-NCSC express additional neural crest stem cell markers and global stem cell genes. To variable degrees and in a donor-dependent manner, hEPI-NCSC express the six essential pluripotency genes C-MYC, KLF4, SOX2, LIN28, OCT-4/POU5F1 and NANOG. hEPI-NCSC can be expanded ex vivo into millions of stem cells that remain mulitpotent and continue to express stem cell genes. The novelty of hEPI-NCSC lies in the combination of their highly desirable traits. hEPI-NCSC are embryonic remnants in a postnatal location, the bulge of hair follicles. Therefore they are readily accessible in the hairy skin by minimal invasive procedure. hEPI-NCSC are multipotent somatic stem cells that can be isolated reproducibly and with high yield. By taking advantage of their migratory ability, hEPI-NCSC can be isolated as a highly pure population of stem cells. hEPI-NCSC can undergo robust ex vivo expansion and directed differentiation. As somatic stem cells, hEPI-NCSC are conducive to autologous transplantation, which avoids graft rejection. Together, these traits make hEPI-NCSC novel and attractive candidates for future cell-based therapies and regenerative medicine

Assessing Internet addiction using the parsimonious Internet addiction components model - a preliminary study [forthcoming]

Internet usage has grown exponentially over the last decade. Research indicates that excessive Internet use can lead to symptoms associated with addiction. To date, assessment of potential Internet addiction has varied regarding populations studied and instruments used, making reliable prevalence estimations difficult. To overcome the present problems a preliminary study was conducted testing a parsimonious Internet addiction components model based on Griffiths’ addiction components (2005), including salience, mood modification, tolerance, withdrawal, conflict, and relapse. Two validated measures of Internet addiction were used (Compulsive Internet Use Scale [CIUS], Meerkerk et al., 2009, and Assessment for Internet and Computer Game Addiction Scale [AICA-S], Beutel et al., 2010) in two independent samples (ns = 3,105 and 2,257). The fit of the model was analysed using Confirmatory Factor Analysis. Results indicate that the Internet addiction components model fits the data in both samples well. The two sample/two instrument approach provides converging evidence concerning the degree to which the components model can organize the self-reported behavioural components of Internet addiction. Recommendations for future research include a more detailed assessment of tolerance as addiction component

The Synthetic Plasmodium falciparum Circumsporozoite Peptide PfCS102 as a Malaria Vaccine Candidate: A Randomized Controlled Phase I Trial

BACKGROUND: Fully efficient vaccines against malaria pre-erythrocytic stage are still lacking. The objective of this dose/adjuvant-finding study was to evaluate the safety, reactogenicity and immunogenicity of a vaccine candidate based on a peptide spanning the C-terminal region of Plasmodium falciparum circumsporozoite protein (PfCS102) in malaria naive adults. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-six healthy malaria-naive adults were randomly distributed into three dose blocks (10, 30 and 100 microg) and vaccinated with PfCS102 in combination with either Montanide ISA 720 or GSK proprietary Adjuvant System AS02A at days 0, 60, and 180. Primary end-point (safety and reactogenicity) was based on the frequency of adverse events (AE) and of abnormal biological safety tests; secondary-end point (immunogenicity) on P. falciparum specific cell-mediated immunity and antibody response before and after immunization. The two adjuvant formulations were well tolerated and their safety profile was good. Most AEs were local and, when systemic, involved mainly fatigue and headache. Half the volunteers in AS02A groups experienced severe AEs (mainly erythema). After the third injection, 34 of 35 volunteers developed anti-PfCS102 and anti-sporozoite antibodies, and 28 of 35 demonstrated T-cell proliferative responses and IFN-gamma production. Five of 22 HLA-A2 and HLA-A3 volunteers displayed PfCS102 specific IFN-gamma secreting CD8(+) T cell responses. Responses were only marginally boosted after the 3(rd) vaccination and remained stable for 6 months. For both adjuvants, the dose of 10 microg was less immunogenic in comparison to 30 and 100 microg that induced similar responses. AS02A formulations with 30 microg or 100 microg PfCS102 induced about 10-folds higher antibody and IFN-gamma responses than Montanide formulations. CONCLUSIONS/SIGNIFICANCE: PfCS102 peptide was safe and highly immunogenic, allowing the design of more advanced trials to test its potential for protection. Two or three immunizations with a dose of 30 microg formulated with AS02A appeared the most appropriate choice for such studies. TRIAL REGISTRATION: Swissmedic.ch 2002 DR 1227

Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA

Big-Data-Driven Materials Science and its FAIR Data Infrastructure

This chapter addresses the forth paradigm of materials research -- big-data driven materials science. Its concepts and state-of-the-art are described, and its challenges and chances are discussed. For furthering the field, Open Data and an all-embracing sharing, an efficient data infrastructure, and the rich ecosystem of computer codes used in the community are of critical importance. For shaping this forth paradigm and contributing to the development or discovery of improved and novel materials, data must be what is now called FAIR -- Findable, Accessible, Interoperable and Re-purposable/Re-usable. This sets the stage for advances of methods from artificial intelligence that operate on large data sets to find trends and patterns that cannot be obtained from individual calculations and not even directly from high-throughput studies. Recent progress is reviewed and demonstrated, and the chapter is concluded by a forward-looking perspective, addressing important not yet solved challenges.Comment: submitted to the Handbook of Materials Modeling (eds. S. Yip and W. Andreoni), Springer 2018/201

Transgenic Potatoes for Potato Cyst Nematode Control Can Replace Pesticide Use without Impact on Soil Quality

Current and future global crop yields depend upon soil quality to which soil organisms make an important contribution. The European Union seeks to protect European soils and their biodiversity for instance by amending its Directive on pesticide usage. This poses a challenge for control of Globodera pallida (a potato cyst nematode) for which both natural resistance and rotational control are inadequate. One approach of high potential is transgenically based resistance. This work demonstrates the potential in the field of a new transgenic trait for control of G. pallida that suppresses root invasion. It also investigates its impact and that of a second transgenic trait on the non-target soil nematode community. We establish that a peptide that disrupts chemoreception of nematodes without a lethal effect provides resistance to G. pallida in both a containment and a field trial when precisely targeted under control of a root tip-specific promoter. In addition we combine DNA barcoding and quantitative PCR to recognise nematode genera from soil samples without microscope-based observation and use the method for nematode faunal analysis. This approach establishes that the peptide and a cysteine proteinase inhibitor that offer distinct bases for transgenic plant resistance to G. pallida do so without impact on the non-target nematode soil community

Evaluation of compliance and outcomes of a management protocol for massive postpartum hemorrhage at a tertiary care hospital in Pakistan

<p>Abstract</p> <p>Background</p> <p>Massive postpartum hemorrhage is a life threatening obstetric emergency. In order to prevent the complications associated with this condition, an organized and step-wise management protocol should be immediately initiated.</p> <p>Methods</p> <p>An evidence based management protocol for massive postpartum hemorrhage was implemented at Aga Khan University Hospital, Karachi, Pakistan after an audit in 2005. We sought to evaluate the compliance and outcomes associated with this management protocol 3 years after its implementation. A review of all deliveries with massive primary postpartum hemorrhage (blood loss ≥ 1500 ml) between January, 2008 to December, 2008 was carried out. Information regarding mortality, mode of delivery, possible cause of postpartum hemorrhage and medical or surgical intervention was collected. The estimation of blood loss was made via subjective and objective assessment.</p> <p>Results</p> <p>During 2008, massive postpartum hemorrhage occurred in 0.64% cases (26/4,052). No deaths were reported. The mean blood loss was 2431 ± 1817 ml (range: 1500 - 9000 ml). Emergency cesarean section was the most common mode of delivery (13/26; 50%) while uterine atony was the most common cause of massive postpartum hemorrhage (14/26; 54%). B-lynch suture (24%) and balloon tamponade (60%) were used more commonly as compared to our previously reported experience. Cesarean hysterectomy was performed in 3 cases (12%) for control of massive postpartum hemorrhage. More than 80% compliance was observed in 8 out of 10 steps of the management protocol. Initiation of blood transfusion at 1500 ml blood loss (89%) and overall documentation of management (92%) were favorably observed in most cases.</p> <p>Conclusion</p> <p>This report details our experience with the practical implementation of a management protocol for massive postpartum hemorrhage at a tertiary care hospital in a developing country. With the exception of arterial embolization, relatively newer, simpler and potentially safer techniques are now being employed for the management of massive postpartum hemorrhage at our institution. Particular attention should be paid to the documentation of the management steps while ensuring a stricter adherence to the formulated protocols and guidelines in order to further ameliorate patient outcomes in emergency obstetrical practice. More audits like the one we performed are important to recognize and rectify any deficiencies in obstetrical practice in developing countries. Dissemination of the same is pivotal to enable an open discourse on the improvement of existing obstetrical strategies.</p

Random-phase approximation and its applications in computational chemistry and materials science

The random-phase approximation (RPA) as an approach for computing the electronic correlation energy is reviewed. After a brief account of its basic concept and historical development, the paper is devoted to the theoretical formulations of RPA, and its applications to realistic systems. With several illustrating applications, we discuss the implications of RPA for computational chemistry and materials science. The computational cost of RPA is also addressed which is critical for its widespread use in future applications. In addition, current correction schemes going beyond RPA and directions of further development will be discussed.Comment: 25 pages, 11 figures, published online in J. Mater. Sci. (2012

Molecular phylogenetics and temporal diversification in the genus Aeromonas based on the sequences of five housekeeping genes

Several approaches have been developed to estimate both the relative and absolute rates of speciation and extinction within clades based on molecular phylogenetic reconstructions of evolutionary relationships, according to an underlying model of diversification. However, the macroevolutionary models established for eukaryotes have scarcely been used with prokaryotes. We have investigated the rate and pattern of cladogenesis in the genus Aeromonas (γ-Proteobacteria, Proteobacteria, Bacteria) using the sequences of five housekeeping genes and an uncorrelated relaxed-clock approach. To our knowledge, until now this analysis has never been applied to all the species described in a bacterial genus and thus opens up the possibility of establishing models of speciation from sequence data commonly used in phylogenetic studies of prokaryotes. Our results suggest that the genus Aeromonas began to diverge between 248 and 266 million years ago, exhibiting a constant divergence rate through the Phanerozoic, which could be described as a pure birth process

Preliminary Target Selection for the DESI Milky Way Survey (MWS)

The DESI Milky Way Survey (MWS) will observe $\ge$8 million stars between $16 < r < 19$ mag, supplemented by observations of brighter targets under poor observing conditions. The survey will permit an accurate determination of stellar kinematics and population gradients; characterize diffuse substructure in the thick disk and stellar halo; enable the discovery of extremely metal-poor stars and other rare stellar types; and improve constraints on the Galaxy's 3D dark matter distribution from halo star kinematics. MWS will also enable a detailed characterization of the stellar populations within 100 pc of the Sun, including a complete census of white dwarfs. The target catalog from the preliminary selection described here is public