Evidence of platelet activation in multiple sclerosis

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Src family kinases, HCK and FGR, associate with local inflammation and tumour progression in colorectal cancer

Background: In colorectal cancer (CRC), inflammatory responses have been reported to associate with patient survival. However, the specific signalling pathways responsible for regulating inflammatory responses are not clear. Src family kinases (SFKs) impact tumourigenic processes, including inflammation. Methods: The relationship between SFK expression, inflammatory responses and cancer specific survival (CSS) in stage I-III CRC patients was assessed using immunohistochemistry on a 272 patient discovery cohort and an extended 822 patient validation cohort. Results: In the discovery cohort, cytoplasmic FGR associated with improved CSS (P=0.019), with membrane HCK (p=0.093) trending towards poorer CSS. In the validation cohort membrane FGR (p=0.016), membrane HCK (p=0.019), and cytoplasmic HCK (p=0.030) all associated with poorer CSS. Both markers also associated with decreased proliferation and cytotoxic T-lymphocytes (all p<0.05). Furthermore, cytoplasmic HCK was an independent prognostic marker compared to common clinical factors. To assess synergy a combine FGR+HCK score was assessed. The membrane FGR+HCK score strengthened associations with poor prognosis (p=0.006), decreased proliferation (p<0.001) and cytotoxic T-lymphocytes (p<0.001) Conclusions: SFKs associate with prognosis and the local inflammatory response in patients with stage I-III CRC. Active membrane FGR and HCK work in parallel to promote tumour progression and down-regulation of the local inflammatory lymphocytic response

Daily reduction of oral malodor with the use of a sonic tongue brush combined with an antibacterial tongue spray in a randomized cross-over clinical investigation

Abstract The objective of this clinical investigation was to test the effectiveness on breath odor of a newly designed sonic tongue brush (TongueCare+, TC). It consists of a soft silicone brush optimally designed based on the tongue's anatomy to remove bacterial biofilm from the tongue's complex surface, and it is coupled with a sonic power toothbrush handle. TC was used in combination with an antibacterial tongue spray (BreathRx, BRx) containing 0.09% cetylpyridinium chloride and 0.7% zinc gluconate. A total of 21 participants with oral malodor exceeding the threshold for recognition took part in this cross-over clinical investigation, which consisted of a single use of four treatment arms with one week washout period in between. The treatments consisted of: (1) TC  +  BRx, (2) TC  +  water, (3) BRx and (4) water. Malodor levels and bacterial density were monitored up to 6 h by organoleptic scoring and selective plating, respectively. The organoleptic score and bacterial density were significantly lower after using TC  +  BRx compared to all alternative treatments at all time points. A significant decrease in both parameters was detected after a single use of TC  +  BRx, from levels characteristic of high oral malodor, to barely noticeable levels after treatment and this was maintained up to 6 h. Moreover, we identified a significant positive correlation between bacterial density and organoleptic score, confirming that bacterial tongue biofilm is the root cause of oral malodor in these subjects. The results of this clinical investigation demonstrated that the combined treatment of a sonic tongue brush with the antibacterial tongue spray is able to deliver more than 6 h of fresh breath following a single use. The clinical investigation was registered at the ISRCTN registry under study identification number ISRCTN38199132

Climacteric Lowers Plasma Levels of Platelet-Derived Microparticles: A Pilot Study in Pre-versus Postmenopausal Women

Background: Climacteric increases the risk of thrombotic events by alteration of plasmatic coagulation. Up to now, less is known about changes in platelet-(PMP) and endothelial cell-derived microparticles (EMP). Methods: In this prospective study, plasma levels of microparticles (MP) were compared in 21 premenopausal and 19 postmenopausal women. Results: No altered numbers of total MP or EMP were measured within the study groups. However, the plasma values of CD61-exposing MP from platelets/megakaryocytes were higher in premenopausal women (5,364 x 10(6)/l, range 4,384-17,167) as compared to postmenopausal women (3,808 x 10(6)/l, range 2,009-8,850; p = 0.020). This differentiation was also significant for the subgroup of premenopausal women without hormonal contraceptives (5,364 x 10(6)/l, range 4,223-15,916; p = 0.047; n = 15). Furthermore, in premenopausal women, higher plasma levels of PMP exposing CD62P were also present as compared to postmenopausal women (288 x 10(6)/l, range 139-462, vs. 121 x 10(6)/l, range 74-284; p = 0.024). This difference was also true for CD63+ PMP levels (281 x 10(6)/l, range 182-551, vs. 137 x 10(6)/l, range 64-432; p = 0.015). Conclusion: Climacteric lowers the level of PMP but has no impact on the number of EMP in women. These data suggest that PMP and EMP do not play a significant role in enhancing the risk of thrombotic events in healthy, postmenopausal women. Copyright (C) 2012 S. Karger AG, Base

The MOSDEF Survey: Differences in SFR and Metallicity for Morphologically-Selected Mergers at z~2

We study the properties of 55 morphologically-identified merging galaxy systems at z~2. These systems are flagged as mergers based on features such as tidal tails, double nuclei, and asymmetry. Our sample is drawn from the MOSFIRE Deep Evolution Field (MOSDEF) survey, along with a control sample of isolated galaxies at the same redshift. We consider the relationships between stellar mass, star formation rate (SFR), and gas-phase metallicity for both merging and non-merging systems. In the local universe, merging systems are characterized by an elevated SFR and depressed metallicity compared to isolated systems at a given mass. Our results indicate SFR enhancement and metallicity deficit for merging systems relative to non-merging systems for a fixed stellar mass at z~2, though larger samples are required to establish these preliminary results with higher statistical significance. In future work, it will be important to establish if the enhanced SFR and depressed metallicity in high-redshift mergers deviate from the "fundamental metallicity relation," as is observed in mergers in the local universe, and therefore shed light on gas flows during galaxy interactions.Comment: 9 pages, 5 figures, 5 figures, accepted to MNRA

The MOSDEF Survey: Differences in SFR and Metallicity for Morphologically-Selected Mergers at z ~ 2

We study the properties of 55 morphologically-identified merging galaxy systems at z ~ 2. These systems are flagged as mergers based on features such as tidal tails, double nuclei, and asymmetry. Our sample is drawn from the MOSFIRE Deep Evolution Field (MOSDEF) survey, along with a control sample of isolated galaxies at the same redshift. We consider the relationships between stellar mass, star formation rate (SFR), and gas-phase metallicity for both merging and non-merging systems. In the local universe, merging systems are characterized by an elevated SFR and depressed metallicity compared to isolated systems at a given mass. Our results indicate SFR enhancement and metallicity deficit for merging systems relative to non-merging systems for a fixed stellar mass at z ~ 2, though larger samples are required to establish these preliminary results with higher statistical significance. In future work, it will be important to establish if the enhanced SFR and depressed metallicity in high-redshift mergers deviate from the "fundamental metallicity relation," as is observed in mergers in the local universe, and therefore shed light on gas flows during galaxy interactions

On-sky speckle nulling through a single-mode fiber with the Keck Planet Imager and Characterizer

The Keck Planet Imager and Characterizer (KPIC) is an instrument at the Keck II telescope that enables high-resolution spectroscopy of directly imaged exoplanets and substellar companions. KPIC uses single-mode fibers to couple the adaptive optics system to Keck's near-infrared spectrometer (NIRSPEC). However, KPIC's sensitivity at small separations is limited by the leakage of stellar light into the fiber. Speckle nulling uses a deformable mirror to destructively interfere starlight with itself, a technique typically used to reduce stellar signal on a focal-plane imaging detector. We present the first on-sky demonstration of speckle nulling through an optical fiber with KPIC, using NIRSPEC to collect exposures that measure speckle phase for quasi-real-time wavefront control while also serving as science data. We repeat iterations of measurement and correction, each using at least 5 exposures. We show a decrease in the on-sky leaked starlight by a factor of 2.6 to 2.8 in the targeted spectral order, at a spatial separation of 2.0 {\lambda}/D in K-band. This corresponds to an estimated factor of 2.6 to 2.8 decrease in the required exposure time to reach a given SNR, relative to conventional KPIC observations. The performance of speckle nulling is limited by instability in the speckle phase: when the loop is opened, the null-depth degrades by a factor of 2 on the timescale of a single phase measurement, which would limit the suppression that can be achieved. Future work includes exploring gradient-descent methods, which may be faster and thereby able to achieve deeper nulls. In the meantime, the speckle nulling algorithm demonstrated in this work can be used to decrease stellar leakage and improve the signal-to-noise of science observations.Comment: 18 pages, 4 figure

Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia

BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as a novel class of RNA due to its diverse mechanism in cancer development and progression. However, the role and expression pattern of lncRNAs in molecular subtypes of B cell acute lymphoblastic leukemia (BCP-ALL) have not yet been investigated. Here, we assess to what extent lncRNA expression and DNA methylation is driving the progression of relapsed BCP-ALL subtypes and we determine if the expression and DNA methylation profile of lncRNAs correlates with established BCP-ALL subtypes. METHODS: We performed RNA sequencing and DNA methylation (Illumina Infinium microarray) of 40 diagnosis and 42 relapse samples from 45 BCP-ALL patients in a German cohort and quantified lncRNA expression. Unsupervised clustering was applied to ascertain and confirm that the lncRNA-based classification of the BCP-ALL molecular subtypes is present in both our cohort and an independent validation cohort of 47 patients. A differential expression and differential methylation analysis was applied to determine the subtype-specific, relapse-specific, and differentially methylated lncRNAs. Potential functions of subtype-specific lncRNAs were determined by using co-expression-based analysis on nearby (cis) and distally (trans) located protein-coding genes. RESULTS: Using an integrative Bioinformatics analysis, we developed a comprehensive catalog of 1235 aberrantly dysregulated BCP-ALL subtype-specific and 942 relapse-specific lncRNAs and the methylation profile of three subtypes of BCP-ALL. The 1235 subtype-specific lncRNA signature represented a similar classification of the molecular subtypes of BCP-ALL in the independent validation cohort. We identified a strong correlation between the DUX4-specific lncRNAs and genes involved in the activation of TGF-β and Hippo signaling pathways. Similarly, Ph-like-specific lncRNAs were correlated with genes involved in the activation of PI3K-AKT, mTOR, and JAK-STAT signaling pathways. Interestingly, the relapse-specific lncRNAs correlated with the activation of metabolic and signaling pathways. Finally, we found 23 promoter methylated lncRNAs epigenetically facilitating their expression levels. CONCLUSION: Here, we describe a set of subtype-specific and relapse-specific lncRNAs from three major BCP-ALL subtypes and define their potential functions and epigenetic regulation. The subtype-specific lncRNAs are reproducible and can effectively stratify BCP-ALL subtypes. Our data uncover the diverse mechanism of action of lncRNAs in BCP-ALL subtypes defining which lncRNAs are involved in the pathogenesis of disease and are relevant for the stratification of BCP-ALL subtypes