Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system.

Targeted recombination was carried out to select mouse hepatitis viruses (MHVs) in a defined genetic background, containing an MHV-JHM spike gene encoding either three heptad repeat 1 (HR1) substitutions (Q1067H, Q1094H, and L1114R) or L1114R alone. The recombinant virus, which expresses spike with the three substitutions, was nonfusogenic at neutral pH. Its replication was significantly inhibited by lysosomotropic agents, and it was highly neuroattenuated in vivo. In contrast, the recombinant expressing spike with L1114R alone mediated cell-to-cell fusion at neutral pH and replicated efficiently despite the presence of lysosomotropic agents; however, it still caused only subclinical morbidity and no mortality in animals. Thus, both recombinant viruses were highly attenuated and expressed viral antigen which was restricted to the olfactory bulbs and was markedly absent from other regions of the brains at 5 days postinfection. These data demonstrate that amino acid substitutions, in particular L1114R, within HR1 of the JHM spike reduced the ability of MHV to spread in the central nervous system. Furthermore, the requirements for low pH for fusion and viral entry are not prerequisites for the highly attenuated phenotype

Stem Cells Expressing Homing Receptors Could be Expanded From Cryopreserved and Unselected Cord Blood

We assessed the cytokine combinations that are best for ex vivo expansion of cord blood (CB) and the increment for cell numbers of nucleated cells, as well as stem cells expressing homing receptors, by an ex vivo expansion of cryopreserved and unselected CB. Frozen leukocyte concentrates (LC) from CB were thawed and cultured at a concentration of 1×105/mL in media supplemented with a combination of SCF (20 ng/mL)+TPO (50 ng/mL)+FL (50 ng/mL)±IL-6 (20 ng/mL)±G-CSF (20 ng/mL). After culturing for 14 days, the expansion folds of cell numbers were as follows: TNC 22.3±7.8~26.3±4.9, CFU-GM 4.7±5.1~11.7±2.6, CD34+CD38- cell 214.0±251.9~464.1±566.1, CD34+CXCR4+ cell 4384.5±1664.7~7087.2±4669.3, CD34+VLA4+ cell 1444.3±1264.0~2074.9±1537.0, CD34+VLA5+ cell 86.2±50.9~113.2±57.1. These results revealed that the number of stem cells expressing homing receptors could be increased by an ex vivo expansion of cryopreserved and unselected CB using 3 cytokines (SCF, TPO, FL) only. Further in vivo studies regarding the engraftment after expansion of the nucleated cells, as well as the stem cells expressing homing receptors will be required

Traces of Archaic Mitochondrial Lineages Persist in Austronesian-Speaking Formosan Populations

Genetic affinities between aboriginal Taiwanese and populations from Oceania and Southeast Asia have previously been explored through analyses of mitochondrial DNA (mtDNA), Y chromosomal DNA, and human leukocyte antigen loci. Recent genetic studies have supported the “slow boat” and “entangled bank” models according to which the Polynesian migration can be seen as an expansion from Melanesia without any major direct genetic thread leading back to its initiation from Taiwan. We assessed mtDNA variation in 640 individuals from nine tribes of the central mountain ranges and east coast regions of Taiwan. In contrast to the Han populations, the tribes showed a low frequency of haplogroups D4 and G, and an absence of haplogroups A, C, Z, M9, and M10. Also, more than 85% of the maternal lineages were nested within haplogroups B4, B5a, F1a, F3b, E, and M7. Although indicating a common origin of the populations of insular Southeast Asia and Oceania, most mtDNA lineages in Taiwanese aboriginal populations are grouped separately from those found in China and the Taiwan general (Han) population, suggesting a prevalence in the Taiwanese aboriginal gene pool of its initial late Pleistocene settlers. Interestingly, from complete mtDNA sequencing information, most B4a lineages were associated with three coding region substitutions, defining a new subclade, B4a1a, that endorses the origin of Polynesian migration from Taiwan. Coalescence times of B4a1a were 13.2 ± 3.8 thousand years (or 9.3 ± 2.5 thousand years in Papuans and Polynesians). Considering the lack of a common specific Y chromosomal element shared by the Taiwanese aboriginals and Polynesians, the mtDNA evidence provided here is also consistent with the suggestion that the proto-Oceanic societies would have been mainly matrilocal

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Welding Distortion Characteristics of Door Openings According to Changing Shape of Stiffener

Welding often results in welding distortion during the assembly process. The welding distortion of thin-plate structures such as the living quarters of ships and offshore installations is a more significant problem than in the case of thick-plate structures. Pre-stressing/heating and fairing, which are additional works to mitigate and control welding distortion, are inevitable, and the construction planning is accordingly delayed. In order to prevent welding distortion and minimize the additional work during the assembly process, increasing the plate thickness and/or the number of stiffeners may be a simple solution, but it may give rise to problems related to cost and weight. In this study, the welding distortion control effect of the type of stiffeners on the door openings of various living quarter structures was investigated using an experimental method and a finite element method. The results showed the feasibility of mitigating and controlling the welding distortion, and the optimum selection of the type of stiffeners was confirmed

Design and clinical developments of aptamer-drug conjugates for targeted cancer therapy

Abstract Background Aptamer has been called “chemical antibody” which displays the specific affinity to target molecules compared to that of antibodies and possesses several therapeutic advantages over antibodies in terms of size, accessibility to synthesis, and modification. Based on the attractive properties, aptamers have been interested in many directions and now are emerged as new target-designed cancer drug. Main body Currently, new types of aptamers have been reported and attracted many scientists’ interesting. Due to simplicity of chemical modification and ready-made molecular engineering, scientists have developed newly designed aptamers conjugated with a wide range of therapeutics, aptamer-drug conjugates; ApDCs, from chemotherapy to phototherapy, gene therapy, and vaccines. ApDCs display synergistic therapeutic effects in cancer treatment. Conclusion In this paper, we reviewed various kinds of ApDCs, i.e., ApDC nucleotide analogs, ApDC by drug intercalation, and ApDC by using chemical linker. Current data prove these ApDCs have sufficient potential to complete clinical development soon. Advanced technology of cancer drug delivery and combination treatment of cancers enables aptamer and conjugated drug (ApDCs) efficient means for targeted cancer treatment that reduces potential toxicity and increases therapeutic efficacy

Flexible transparent electrodes for organic light-emitting diodes

The use of flexible organic light-emitting diodes (OLEDs) for the next-generation displays and solid-state lightings has been considered, but the widely used transparent conducting electrode (TCE), indium?tin-oxide (ITO), should be replaced by flexible electrodes due to its brittleness and increasing cost. Therefore, many kinds of alternative TCEs have been increasingly studied. In this paper, the properties and applications of the candidate transparent flexible electrodes classified into four categories (conducting polymer, silver nanowire, carbon nanotube and graphene) are described. This paper finally suggests how to develop alternative TCEs for replacing the conventional ITO electrode.

Adhesion Improvement of Solvent-Free Pressure-Sensitive Adhesives by Semi-IPN Using Polyurethanes and Acrylic Polymers

To improve the peel strength and holding time of polypropylene glycol (PPG)-based pressure-sensitive adhesives (PSAs), a semi-interpenetrating polymer network (semi-IPN) was prepared using acrylic polymers. In addition, to prevent air pollution due to volatile organic compound emissions and avoid the degradation of physical properties due to a residual solvent, the PPG-based semi-IPN PSAs were fabricated by an eco-friendly solvent-free method using an acrylic monomer instead of an organic solvent. PPG-based semi-IPN PSAs with different hard segment contents (2.9–17.2%) were synthesized; their holding time was found to depend on the hard segment contents. The peel strength was improved because of the formation of the semi-IPN structure. Moreover, the high degree of hard domain formation in the semi-IPN PSA, derived from the increase in the hard segment content using a chain extender, resulted in a holding time improvement. We believe that the as-prepared PSAs can be used in various applications that require high creep resistance