Saline irrigation spells relief for sinusitis sufferers

Recommend nasal irrigation to patients with chronic rhinosinusitis. Large-volume, low- pressure saline irrigation decreases the severity and frequency of symptoms. Stength of recommendation: B: Single well-done randomized controlled trial (RCT)

CRYOTE (Cryogenic Orbital Testbed) Concept

Demonstrating cryo-fluid management (CFM) technologies in space is critical for advances in long duration space missions. Current space-based cryogenic propulsion is viable for hours, not the weeks to years needed by space exploration and space science. CRYogenic Orbital TEstbed (CRYOTE) provides an affordable low-risk environment to demonstrate a broad array of critical CFM technologies that cannot be tested in Earth's gravity. These technologies include system chilldown, transfer, handling, health management, mixing, pressure control, active cooling, and long-term storage. United Launch Alliance is partnering with Innovative Engineering Solutions, the National Aeronautics and Space Administration, and others to develop CRYOTE to fly as an auxiliary payload between the primary payload and the Centaur upper stage on an Atlas V rocket. Because satellites are expensive, the space industry is largely risk averse to incorporating unproven systems or conducting experiments using flight hardware that is supporting a primary mission. To minimize launch risk, the CRYOTE system will only activate after the primary payload is separated from the rocket. Flying the testbed as an auxiliary payload utilizes Evolved Expendable Launch Vehicle performance excess to cost-effectively demonstrate enhanced CFM

The small heat shock protein B8 (HSPB8) confers resistance to bortezomib by promoting autophagic removal of misfolded proteins in multiple myeloma cells

Velcade is one of the inescapable drug to treat patient suffering from multiple myeloma (MM) and resistance to this drug represents a major drawback for patients. However, the mechanisms underlying velcade resistance remain incompletely understood. We derived several U266 MM cell clones that resist to velcade. U266-resistant cells were resistant to velcade-induced cell death but exhibited a similar sensitivity to various proapoptotic stimuli. Careful analysis of proteosomal subunits and proteasome enzymatic activities showed that neither the composition nor the activity of the proteasome was affected in velcade-resistant cells. Elimination of velcade-induced poly-ubiquitinated proteins and protein aggregates was drastically stimulated in the resistant cells and correlated with increased cell survival. Inhibition of the lysosomal activity in velcade-resistant cells resulted in an increase of cell aggregates and decrease survival, indicating that aggregates are eliminated through lysosomal degradation. In addition, pangenomic profiling of velcade-sensitive and resistant cells showed that the small heat shock protein HSPB8 was overexpressed in resistant cells. Finally, gain and loss of function experiment demonstrated that HSPB8 is a key factor for velcade resistance. In conclusion, HSPB8 plays an important role for the elimination of aggregates in velcade-resistant cells that contributes to their enhanced survival

Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis

International audienceABSTRACT: BACKGROUND: In severe obesity, as well as in normal development, the growth of adipose tissue is the result of an increase in adipocyte size and numbers, which is underlain by the stimulation of adipogenic differentiation of precursor cells. A better knowledge of the pathways that regulate adipogenesis is therefore essential for an improved understanding of adipose tissue expansion. As microRNAs (miRNAs) have a critical role in many differentiation processes, our study aimed to identify the role of miRNA-mediated gene silencing in the regulation of adipogenic differentiation. RESULTS: We used deep sequencing to identify small RNAs that are differentially expressed during adipogenesis of adipose tissue-derived stem cells. This approach revealed the un-annotated miR-642a-3p as a highly adipocyte-specific miRNA. We then focused our study on the miR-30 family, which was also up-regulated during adipogenic differentiation and for which the role in adipogenesis had not yet been elucidated. Inhibition of the miR-30 family blocked adipogenesis, whilst over-expression of miR-30a and miR-30d stimulated this process. We additionally showed that both miR-30a and miR-30d target the transcription factor RUNX2, and stimulate adipogenesis via the modulation of this major regulator of osteogenesis. CONCLUSIONS: Overall, our data suggest that the miR-30 family plays a central role in adipocyte development. Moreover, as adipose tissue-derived stem cells can differentiate into either adipocytes or osteoblasts, the down-regulation of the osteogenesis regulator RUNX2 represents a plausible mechanism by which miR-30 miRNAs may contribute to adipogenic differentiation of adipose tissue-derived stem cells

Case 28-2019: A 22-Year-Old Woman with Dyspnea and Chest Pain

Case report on a 22-year-old woman who was seen in the pediatric pulmonary clinic of this hospital because of chest pain, cough, and dyspnea on exertion

Spt6 levels are modulated by PAAF1 and proteasome to regulate the HIV-1 LTR

<p>Abstract</p> <p>Background</p> <p>Tat-mediated activation of the HIV-1 promoter depends upon a proteasome-associated factor, PAAF1, which dissociates 26S proteasome to produce 19S RP that is essential for transcriptional elongation. The effect of PAAF1 on proteasome activity could also potentially shield certain factors from proteolysis, which may be implicated in the transcriptional co-activator activity of PAAF1 towards the LTR.</p> <p>Results</p> <p>Here, we show that Spt6 is targeted by proteasome in the absence of PAAF1. PAAF1 interacts with the N-terminus of Spt6, suggesting that PAAF1 protects Spt6 from proteolysis. Depletion of either PAAF1 or Spt6 reduced histone occupancy at the HIV-1 promoter, and induced the synthesis of aberrant transcripts. Ectopic Spt6 expression or treatment with proteasome inhibitor partially rescued the transcription defect associated with loss of PAAF1. Transcriptional profiling followed by ChIP identified a subset of cellular genes that are regulated in a similar fashion to HIV-1 by Spt6 and/or PAAF1, including many that are involved in cancer, such as BRCA1 and BARD1.</p> <p>Conclusion</p> <p>These results show that intracellular levels of Spt6 are fine-tuned by PAAF1 and proteasome, which is required for HIV-1 transcription and extends to cellular genes implicated in cancer.</p

Cryogenic Orbital Testbed (CRYOTE) Ground Test Article, Final Report

Liquid propulsion has been used since Robert Goddard started developing a liquid oxygen (LO2) and gasoline powered rocket and fired it in 1923 (Ref. 1). In the following decades engineers settled on the combination of liquid hydrogen (LH2) and LO2 as the most efficient propellant combination for in-space travel. Due to their low temperatures (LH2 at 20 K and LO2 at 90 K), they require special handling and procedures. General Dynamics began developing LO2 and LH2 upper stages in 1956 in the form of Centaur, these efforts were soon funded by the Department of Defense in conjunction with NASA (beginning in 1958) (Ref. 2). Meanwhile NASA also worked with McDonnell Douglas to develop the SIV-B stage for the Saturn V rocket. In the subsequent years, the engineers were able to push the Centaur to up to 9 hr of orbital lifetime and the SIV-B to up to 6 hr. Due to venting the resultant boil-off from the high heat loads through the foam insulation on the upper stages, both vehicles remained in a settled configuration throughout the flights, thus the two phases of propellant (liquid and vapor) were separated at a known location. The one exception to this were the Titan/Centaur missions, which thanks to the lower boil-off using three layers of multilayer insulation (MLI), were able to coast unsettled for up to 5.25 hr during direct geosynchronous orbit insertion missions. In the years since there has been a continuous effort to extend the life of these upper stages from hours to days or even months