Direct conversion of astrocytes into neuronal cells by drug cocktail

Direct conversion of astrocytes into neuronal cells by drug cocktail Cell Research advance online publication 2 October 2015; doi:10.1038/cr.2015.120 Dear Editor, Neurological disorder is one of the greatest threats to public health according to the World Health Organization. Because neurons have little or no regenerative capacity, conventional therapies for neurological disorders yielded poor outcomes. While the introduction of exogenous neural stem cells or neurons holds promise, many challenges still need to be tackled, including cell resource, delivery strategy, cell integration and cell maturation. Reprogramming of fibroblasts into induced pluripotent stem cells or directly into desirable neuronal cells by transcription factors (TFs) or small molecules can solve some problems, but other issues remain to be addressed, including safety, conversion efficiency and epigenetic memory [1, 2]. Astrocytes are considered to be the ideal starting candidate cell type for generating new neurons, due to their proximity in lineage distance to neurons and ability to proliferate after brain damage. Many studies have already revealed that astrocytes of the central nervous system can be reprogrammed into induced neuronal cells by virus-mediated overexpression of specific TFs in vitro and in vivo [3-6]. However, application of this virus-mediated direct conversion is still limited due to concerns on clinical safety. We have previously reported direct conversion of somatic cells into neural progenitor cells (NPCs) in vitro by cocktail of small molecules under hypoxia [7]. Here we set out to explore whether astrocytes can be induced into neuronal cells by the chemical cocktail in vitro

A giant hemolymphangioma of the pancreas in a 20-year-old girl: a report of one case and review of the literature

<p>Abstract</p> <p>Background</p> <p>Hemolymphangioma of the pancreas is a very rare benign tumor. There were only six reports of this disease until December 2008. Herein, we report a case of giant hemolymphangioma of the pancreas in a 20-year-old girl.</p> <p>Case presentation</p> <p>We describe a 20-year-old girl who presented with a mass in abdominal cavity and epigastric discomfort about a week. Physical examination showed a great abdominal mass. Abdominal computed tomography showed extrinsic duodenal compression due to a large retroperitoneal tumor possibly arising from pancreas. The tumor enucleation was performed and a diagnosis of hemolymphangioma of the pancreas was made. The patient had a complication of chylous leakage, which was successfully managed. The patient is alive and well, after 26 months of follow-up, with no complaints or recurrence.</p> <p>Conclusion</p> <p>From this case and literature, we can conclude that hemolymphangioma of the pancreas in adult is a rare benign tumor, and accurate diagnosis can not be preoperatively established. Tumor resection should be performed whenever possible. The risk of recurrence seems very low.</p

Precision Spectroscopy and Nuclear Structure Parameters in 7Li+ ion

The optical Ramsey technique is used to obtain precise measurements of the hyperfine splittings in the 2\,^3\!S_1 and 2\,^3\!P_J states of $^7$Li$^+$. Together with bound-state quantum electrodynamic theory, the Zemach radius and quadrupole moment of the $^7$Li nucleus are determined to be $3.35(1)$~fm and $-3.86(5)$~fm$^2$ respectively, with the quadrupole moment deviating from the recommended value of $-4.00(3)$~fm$^2$ by $1.75\sigma$. Furthermore, we determine the quadrupole moment ratio of $^6$Li to $^7$Li as $0.101(13)$, exhibiting a $6\sigma$ deviation from the previous measured value of $0.020161(13)$ by LiF molecular spectroscopy. The results taken together provide a sensitive test of nuclear structure models

Anti-tumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma is difficult to diagnose early, and most patients are already in the late stages of the disease when they are admitted to hospital. The total 5-year survival rate is less than 5%. Recent studies have showed that brucine has a good anti-tumor effect, but high toxicity, poor water solubility, short half-life, narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study evaluated the effects of brucine immuno-nanoparticles (BIN) on hepatocellular carcinoma. MATERIALS AND METHODS: Anionic polymerization, chemical modification technology, and phacoemulsification technology were used to prepare a carboxylated polyethylene glycol-polylactic acid copolymer carrier material. Chemical coupling technology was utilized to develop antihuman AFP McAb-polyethylene glycol-polylactic acid copolymer BIN. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these immune-nanoparticles were studied in vitro. The targeting, and growth, invasion, and metastasis inhibitory effects of this treatment on liver cancer SMMC-7721 cells were tested. RESULTS: BIN were of uniform size with an average particle size of 249 ± 77 nm and zeta potential of -18.7 ± 4.19 mV. The encapsulation efficiency was 76.0% ± 2.3% and the drug load was 5.6% ± 0.2%. Complete uptake and even distribution around the liver cancer cell membrane were observed. CONCLUSION: BIN had even size distribution, was stable, and had a slow-releasing effect. BIN targeted the cell membrane of the liver cancer cell SMMC-7721 and significantly inhibited the growth, adhesion, invasion, and metastasis of SMMC-7721 cells. As a novel drug carrier system, BIN are a potentially promising targeting treatment for liver cancer

Evolutionary trajectories of snake genes and genomes revealed by comparative analyses of five-pacer viper

Snakes have numerous features distinctive from other tetrapods and a rich history of genome evolution that is still obscure. Here, we report the high-quality genome of the five-pacer viper, Deinagkistrodon acutus, and comparative analyses with other representative snake and lizard genomes. We map the evolutionary trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion, and many viper TEs show brain-specific gene expression along with their nearby genes. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes and also functional degeneration of genes associated with vision and hearing. Lineage-specific relaxation of functional constraints on respective Hox and Tbx limb-patterning genes supports fossil evidence for a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we infer that the ZW sex chromosome pair had undergone at least three recombination suppression events in the ancestor of advanced snakes. These results altogether forge a framework for our deep understanding into snakes' history of molecular evolution

Structural Insights into the Stability and Recognition Mechanism of the Antiquinalphos Nanobody for the Detection of Quinalphos in Foods

Nanobodies (Nbs) have great potential in immunoassays due to their exceptional physicochemical properties. With the immortal nature of Nbs and the ability to manipulate their structures using protein engineering, it will become increasingly valuable to understand what structural features of Nbs drive high stability, affinity, and selectivity. Here, we employed an anti-quinalphos Nb as a model to illustrate the structural basis of Nbs' distinctive physicochemical properties and the recognition mechanism. The results indicated that the Nb-11A-ligand complexes exhibit a "tunnel" binding mode formed by CDR1, CDR2, and FR3. The orientation and hydrophobicity of small ligands are the primary determinants of their diverse affinities to Nb-11A. In addition, the primary factors contributing to Nb-11A's limited stability at high temperatures and in organic solvents are the rearrangement of the hydrogen bonding network and the enlargement of the binding cavity. Importantly, Ala 97 and Ala 34 at the active cavity's bottom and Arg 29 and Leu 73 at its entrance play vital roles in hapten recognition, which were further confirmed by mutant Nb-F3. Thus, our findings contribute to a deeper understanding of the recognition and stability mechanisms of anti-hapten Nbs and shed new light on the rational design of novel haptens and directed evolution to produce high-performance antibodies

Wireless Sensor Technologies and Applications

Recent years have witnessed tremendous advances in the design and applications of wirelessly networked and embedded sensors. Wireless sensor nodes are typically low-cost, low-power, small devices equipped with limited sensing, data processing and wireless communication capabilities, as well as power supplies. They leverage the concept of wireless sensor networks (WSNs), in which a large (possibly huge) number of collaborative sensor nodes could be deployed. As an outcome of the convergence of micro-electro-mechanical systems (MEMS) technology, wireless communications, and digital electronics, WSNs represent a significant improvement over traditional sensors. In fact, the rapid evolution of WSN technology has accelerated the development and deployment of various novel types of wireless sensors, e.g., multimedia sensors. Fulfilling Moore’s law, wireless sensors are becoming smaller and cheaper, and at the same time more powerful and ubiquitous. [...

Understanding the Psychological Motives Behind Microblogging

Abstract. This research aims to understand the psychological motives behind microblogging. We conducted two studies to investigate if social exclusion and existential anxiety would lead to a high tendency to microblog. Our results show that participants did not use microblogging to satisfy their needs for social connection and affiliation, but highly extraverted participants did use it to relieve their existential anxiety

The gut microbiome and metabolites are altered and interrelated in patients with functional constipation

IntroductionGut microbiota and metabolites have been identified to contribute to the pathogenesis of functional constipation (FC); however, the underlying mechanism(s) have not been elucidated, and the relationship between the gut microbiota and metabolites in FC has received limited attention in the literature.Methods16S rDNA sequencing and non-targeted metabolomic detection based on liquid chromatography-mass spectrometry (LC–MS/MS) technologies were combined to analyze the altered gut microbiome and metabolic profile of fecal samples from FC patients and healthy individuals (healthy control; HC).ResultsThe richness and diversity of gut microbiota significantly (p &lt; 0.01) increased in FC patients. Compared to the HC group, 18 genera, including Intestinibacter, Klebsiella, and Akkermansia, exhibited statistically significant changes (p &lt; 0.05). Metabolic analysis showed that metabolic profiles were also markedly altered with 79 metabolites, such as (-)-caryophyllene oxide, chenodeoxycholic acid, and biliverdin, indicating significant inter-group differences (p &lt; 0.05). Besides, the primary bile acid biosynthesis, as well as the metabolic profile of porphyrin and chlorophyll, were the most dominant enriched pathways (FDR &lt; 0.01), in which chenodeoxycholic acid and biliverdin were significantly enriched, respectively. Correlation analysis demonstrated a strong relationship between 10 genera and 19 metabolites (r &gt; 0.6, FDR &lt; 0.05), and notably, Intestinibacter showed a negative correlation with biliverdin (FDR &lt; 0.001), which highlighted the interplay of the gut microbiota and metabolites in the pathogenesis of FC.ConclusionOur research describes the characteristics of the gut microbiota and metabolic profiles and the correlation between the gut microbiota and metabolites in FC patients. This may contribute to the understanding of the underlying mechanisms involved in FC pathogenesis and may provide novel insights into therapeutic interventions