MiR-379 inhibits proliferation and induces apoptosis in multiple myeloma by targeting Y-box binding protein 1

Purpose: To determine the effect of miR-379 in multiple myeloma.Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the expression of miR-379 in multiple myeloma cells. The effect of miR-379 on multiple myeloma progression was investigated by cell counting, bromodeoxyuridine staining, flow cytometry and Western blot analysis. A potential target for miR-379 was determined using a luciferase reporter assay.Results: MiR-379 expression was reduced in multiple myeloma cells, while over-expression of miR-379 increased both cell viability and proliferation of these cells (p < 0.05). Moreover, miR-379 blocked cell cycle multiple myeloma cells and promoted apoptosis by decreasing Bcl-2 expression, and increasing the expression of cleaved caspase-3 and Bax. MiR-379 bound to Y-box binding protein 1 (YBX1) and reduced YBX1 mRNA and protein expression in multiple myeloma cells (p < 0.05).Conclusion: A YBX1-mediated tumor-suppressive role for miR-379 in multiple myeloma cells has been identified, suggesting a potential strategy for the treatment of multiple myeloma. Keywords: MiR-379, Y-box binding protein 1, Multiple myeloma, Proliferation, Apoptosi

VACCINE STABILIZATION – RESEARCH, COMMERCIALIZATION, AND IMPACT

Improving the stability of vaccines and removing vaccines from refrigerated storage for all or part of their shelf life have been proposed as strategies to help ensure vaccine effectiveness and to mitigate cold chain storage capacity constraints and escalating costs associated with the introduction of new vaccines into developing countries. Over the last six years, PATH has conducted research on stabilization of measles, Haemophilus influenzae type b (Hib), hepatitis B, enterotoxgenic Escherichia coli, conjugate meningococcal A, and pentavalent (Diphtheria-Tetanus-Pertussis-hepatitis B-Hib) vaccines in collaboration with 22 technical partners and 10 vaccine development groups. Results will be shared and include marked improvement to the stability of hepatitis B vaccine (12 months at 37 degrees C), more modest improvement to the stability of measles vaccine (8 weeks at 37 degrees C), and development of a freeze-protection method applicable to all aluminum adjuvant-containing vaccines. Improved vaccine stability has an inherent value to manufacturers (e.g., improved bulk production efficiencies, reduced risk of recalls when the cold chain is breached during shipment, and reduced shipping and storage costs). Regardless, a return on investment for vaccine producers serving the highly price-sensitive developing-country markets is likely to be very dependent on the willingness of the customers to bear additional cost of goods. Mechanisms are needed to communicate desired stability profiles for new vaccines to vaccine developers and to incentivize vaccine developers to enhance product stability. In addition, dialogue between industry and the public sector (e.g., via the Vaccine Presentation and Packaging Advisory Group) is needed to analyze the inevitable trade-offs that occur between one desirable product attribute and another during product development. Economic analyses of the incremental health and programmatic cost impacts of introducing four thermostable vaccines into immunization programs in Cambodia, Ghana, and Bangladesh show the potential for thermostable formulations to be cost-effective in low-resource settings. In addition, real efforts are underway through Project Optimize, a collaborative effort between the World Health Organization and PATH, to determine how vaccines can best be stored and distributed in the future. Project Optimize is seeking to answer the logistical, policy, regulatory, and cost issues related to labeling and storage of thermostable vaccines at controlled ambient temperatures for part of their shelf life to enable outreach and minimize storage/transport costs. This work will be critical to understanding the full value of thermostable vaccines

Ex Perimental Study on Water Absorption of Coal Under Different Pressure Source Conditions

AbstractIn order to study the effect of pressure on the water absorption capability of coal, the water injection experiments of two coal samples were done under different pressure source conditions and room temperature by using self-designed pressurized water device. The experimental results show that pressure has a positive effect on water absorbability; water absorbability gets large as the pressure increases; the earlier water absorbability of coal is rapid, and the water absorbability of coal displays a similar Langmuir-isothermal adsorption curve with the changes of time, and it has saturated water absorbability. The water injection pressure is higher, which not only strengthened the ability of expanding seepage space, but also developed the transporting water and storage water space. The later water absorption curve of coal becomes weaker, and water adsorption process is mainly influenced by capillary force. The pressure water only supplies provisions and time is the main influential factor

Effects of Thinning Intensities on Soil Infiltration and Water Storage Capacity in a Chinese Pine-Oak Mixed Forest

Thinning is a crucial practice in the forest ecosystem management. The soil infiltration rate and water storage capacity of pine-oak mixed forest under three different thinning intensity treatments (15%, 30%, and 60%) were studied in Qinling Mountains of China. The thinning operations had a significant influence on soil infiltration rate and water storage capacity. The soil infiltration rate and water storage capacity in different thinning treatments followed the order of control (nonthinning): <60%, <15%, and <30%. It demonstrated that thinning operation with 30% intensity can substantially improve soil infiltration rate and water storage capacity of pine-oak mixed forest in Qinling Mountains. The soil initial infiltration rate, stable infiltration rate, and average infiltration rate in thinning 30% treatment were significantly increased by 21.1%, 104.6%, and 60.9%, compared with the control. The soil maximal water storage capacity and noncapillary water storage capacity in thinning 30% treatment were significantly improved by 20.1% and 34.3% in contrast to the control. The soil infiltration rate and water storage capacity were significantly higher in the surface layer (0~20 cm) than in the deep layers (20~40 cm and 40~60 cm). We found that the soil property was closely related to soil infiltration rate and water storage capacity

AFLP ANALYSIS OF POPULATIONS OF HALIOTIS DISCUS HANNAI, HALIOTIS GIGANTEA, AND THEIR HYBRIDS

Amplified fragment length polymorphism (AFLP) analysis of the population genetic structure and genetic diversity of Haliotis discus hannai (D), Haliotis gigantea (G), and their reciprocal hybrids D female x G male (DG) and G female x D male (GD) was carried out in this study. A total of 479 unambiguous and highly repeatable AFLP markers, 311 of which (64.93%) were polymorphic, were obtained using 7 primer combinations. The reciprocal hybrids inherited bands from both parents, indicating that the hybrids were truly heterogeneous. The Shannon diversity index for D, G, and their reciprocal hybrid populations DG and GD was 0.169 +/- 0.188, 0.211 +/- 0.227, 0.236 +/- 0.267, and 0.231 +/- 0.242, respectively. Analysis of molecular variance revealed that 29.58% of the variance was among populations, whereas 71.42% of variance was within populations. Genetic distance was maximum (0.681) between D and G, and was minimum (0.482) between GD and G. The 4 populations were clustered into 2 major clades using the unweighted pair group method with arithmetic mean. All genetic parameters indicated that there was plentiful genetic diversity in the reciprocal hybrids of D X G. Results of this study suggest that these AFLP markers can be used in the future to enhance current breeding practices in abalone culture because of the large numbers of polymorphic markers

Chronic Voluntary Alcohol Drinking Causes Anxiety-Like Behavior, Thiamine Deficiency, and Brain Damage of Female Crossed High Alcohol Preferring Mice

The central nervous system is vulnerable to chronic alcohol abuse, and alcohol dependence is a chronically relapsing disorder which causes a variety of physical and mental disorders. Appropriate animal models are important for investigating the underlying cellular and molecular mechanisms. The crossed High Alcohol Preferring mice prefer alcohol to water when given free access. In the present study, we used female cHAP mice as a model of chronic voluntary drinking to evaluate the effects of alcohol on neurobehavioral and neuropathological changes. The female cHAP mice had free-choice access to 10% ethanol and water, while control mice had access to water alone at the age of 60-day-old. The mice were exposed to alcohol for 7 months then subjected to neurobehavioral tests including open field (OF), elevated plus maze (EPM), and Morris water maze (MWM). Results from OF and EPM tests suggested that chronic voluntary drinking caused anxiety-like behaviors. After behavior tests, mice were sacrificed, and brain tissues were processed for biochemical analyses. Alcohol altered the levels of several neurotransmitters and neurotrophic factors in the brain including gamma-Aminobutyric acid (GABA), corticotropin-releasing factor, cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor. Alcohol increased the expression of neuroinflammation markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and C-C chemokine receptor 2 (CCR2). Alcohol also induced cleaved caspase-3 and glial fibrillary acidic protein, indicative of neurodegeneration and gliosis. In addition, alcohol inhibited the expression of thiamine transporters in the brain and reduced thiamine levels in the blood. Alcohol also caused oxidative stress and endoplasmic reticulum (ER) stress, and stimulated neurogenesis

Formulation development of a recombinant protein based non-replicating rotavirus (NRRV) vaccine candidate: Antigen-adjuvant-preservative interactions

Rotavirus is the leading cause of acute diarrhea and gastroenteritis among infants and young children worldwide. Over 215,000 children under five years of age die from rotavirus infection each year, mostly in developing world1. Currently two live attenuated oral rotavirus vaccines are available globally (Rotarix® and RotaTeq®) to reduce the burden of this disease with an efficacy of \u3e90% in developed countries2. Vaccine efficacy is lower, however, in developing countries due to a variety of factors3. To this end, a non-replicating rotavirus (NRRV) vaccine candidate, containing three recombinant protein antigens (P2-VP8-P[4], P2-VP8-P[6] and P2-VP8-P[8]), is being developed by PATH and its partners as a trivalent vaccine for use in the developing world4. This trivalent rotavirus vaccine candidate includes the three antigens from the most prevalent serotypes associated with \u3e90% of rotavirus gastroenteritis worldwide. In the present study, the following formulation development issues were examined: (1) establish stability-indicating physicochemical assays for a NRRV protein antigen (P[8]) bound to an aluminum hydroxide adjuvant (Alhydrogel®), which include primary and higher-order structures, chemical and conformational stability of the protein on Alhydrogel, and the ability to desorb the antigen from Alhydrogel; (2) examine the adsorptive capacity and coefficients of Alhydrogel® for the P[8] antigen in several candidate drug product formulations; (3) investigate the effects of binding to Alhydrogel® and the addition of two antimicrobial preservatives (2-phenoxyethanol or thimerosal) on the structural integrity and conformational stability of P[8], the latter of which were found to be potent destabilizers of the antigen; and (4) monitor the real-time and accelerated storage stability over 3 months of P[8] bound to Alhydrogel® in several candidate formulations with and without thimerosal at different temperatures. In the absence of preservative, the P[8] protein antigen was overall stable with only a small amount of Asn deamidation observed in samples stored under real-time (4˚C) or accelerated (25˚C) temperatures. Similarly, little (if any) changes were observed in the real-time stability of the antigen on Alhydrogel® in the presence of thimerosal. Under accelerated storage temperatures (25 or 37˚C) however, the preservative caused an increase in inter-molecular disulfide bonding, decrease of apparent enthalpy as measured by DSC, and a decrease in in-vitro antigenicity. Similar stability studies are currently ongoing with the P[4] and P[6] protein antigens. Acknowledgements: Funding provided by the Bill & Melinda Gates Foundation References: 1. Tate et al 2016. Clinical Infectious Diseases 62:S96-S105 2. Tissera et al. 2017. Human Vaccines & Immunotherapeutics 13(4):921-927 3. Glass et al. 2014. Journal of Infection 68: S9-S18. 4. Groome et al. 2017. Lancet Infectious Diseases17(8): 843-853

Head and Neck Cancer Tumor Segmentation Using Support Vector Machine in Dynamic Contrast-Enhanced MRI

Objective. We aimed to propose an automatic method based on Support Vector Machine (SVM) and Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to segment the tumor lesions of head and neck cancer (HNC). Materials and Methods. 120 DCE-MRI samples were collected. Five curve features and two principal components of the normalized time-intensity curve (TIC) in 80 samples were calculated as the dataset in training three SVM classifiers. The other 40 samples were used as the testing dataset. The area overlap measure (AOM) and the corresponding ratio (CR) and percent match (PM) were calculated to evaluate the segmentation performance. The training and testing procedure was repeated for 10 times, and the average performance was calculated and compared with similar studies. Results. Our method has achieved higher accuracy compared to the previous results in literature in HNC segmentation. The average AOM with the testing dataset was 0.76 ± 0.08, and the mean CR and PM were 79 ± 9% and 86 ± 8%, respectively. Conclusion. With improved segmentation performance, our proposed method is of potential in clinical practice for HNC