26 research outputs found
Homotopy Normal Maps
Normal maps between discrete groups were characterized [FS]
as those which induce a compatible topological group structure on the homotopy
quotient . Here we deal with topological group (or loop) maps
being normal in the same sense as above and hence forming a
homotopical analogue to the inclusion of a topological normal subgroup in a
reasonable way.
We characterize these maps by a compatible simplicial loop space structure on
, invariant under homotopy monoidal functors, e.g.
Localizations and Completions. In the course of characterizing homotopy
normality, we define a notion of a "homotopy action" similar to an
action on a space, but phrased in terms of Segal's 'special spaces'
and seem to be of importance on its own right. As an application of the
invariance of normal maps, we give a very short proof to a theorem of Dwyer and
Farjoun namely that a localization by a suspended map of a principal fibration
of connected spaces is again principal.Comment: This paper appeared under "Matan Prezma"; later papers of the author
appear under "Matan Prasma
Cell death induction of chronic lymphocytic leukemia lymphocytes using VDAC1-based peptides: A novel therapeutic approach
Giant ovarian mucinous cystadenocarcinoma: A case report
Abstract Giant ovarian tumors are rare in the present day due to the early diagnosis and treatment. However, owing to the large size, it can often compress the inferior vena cava and sudden decompression of it during the removal can lead to hemodynamic instability with disastrous outcomes
Human Placenta-Derived Stromal Cells Rescue Mice from Radiation-Induced Bone Marrow Failure: A Cytof-Based Mechanistic Analysis
Novel Biomarker Proteins in Chronic Lymphocytic Leukemia: Impact on Diagnosis, Prognosis and Treatment
<div><p>In many cancers, cells undergo re-programming of metabolism, cell survival and anti-apoptotic defense strategies, with the proteins mediating this reprogramming representing potential biomarkers. Here, we searched for novel biomarker proteins in chronic lymphocytic leukemia (CLL) that can impact diagnosis, treatment and prognosis by comparing the protein expression profiles of peripheral blood mononuclear cells from CLL patients and healthy donors using specific antibodies, mass spectrometry and binary logistic regression analyses and other bioinformatics tools. Mass spectrometry (LC-HR-MS/MS) analysis identified 1,360 proteins whose expression levels were modified in CLL-derived lymphocytes. Some of these proteins were previously connected to different cancer types, including CLL, while four other highly expressed proteins were not previously reported to be associated with cancer, and here, for the first time, DDX46 and AK3 are linked to CLL. Down-regulation expression of two of these proteins resulted in cell growth inhibition. High DDX46 expression levels were associated with shorter survival of CLL patients and thus can serve as a prognosis marker. The proteins with modified expression include proteins involved in RNA splicing and translation and particularly mitochondrial proteins involved in apoptosis and metabolism. Thus, we focused on several metabolism- and apoptosis-modulating proteins, particularly on the voltage-dependent anion channel 1 (VDAC1), regulating both metabolism and apoptosis. Expression levels of Bcl-2, VDAC1, MAVS, AIF and SMAC/Diablo were markedly increased in CLL-derived lymphocytes. VDAC1 levels were highly correlated with the amount of CLL-cancerous CD19+/CD5+ cells and with the levels of all other apoptosis-modulating proteins tested. Binary logistic regression analysis demonstrated the ability to predict probability of disease with over 90% accuracy. Finally, based on the changes in the levels of several proteins in CLL patients, as revealed from LC-HR-MS/MS, we could distinguish between patients in a stable disease state and those who would be later transferred to anti-cancer treatments. The over-expressed proteins can thus serve as potential biomarkers for early diagnosis, prognosis, new targets for CLL therapy, and treatment guidance of CLL, forming the basis for personalized therapy.</p></div
Hierarchical clustering and functional analysis of proteins expression in PBMCs obtained from healthy controls and CLL patients.
<p>The protein expression profiles of PBMCs obtained from healthy donors and CLL patients were analyzed by LC-HR-MS/MS as described under Materials and Methods. <b>A.</b> Hierarchical clustering based on the expression pattern of all 2,441 detected proteins with at least 1 unique peptide is presented. Healthy (white) and CLL (grey) are indicated. The color scale of the standardized expression values is shown on the right. <b>B.</b> Significantly enriched pathways associated with differentially expressed proteins in CLL, with their enrichment p-value, are presented. The number of proteins related to each pathway is indicated inside the chart. <b>C</b>. Significantly enriched functional groups based on the DAVID functional analysis are presented, with their enrichment p-value. The number of proteins related to each functional group is indicated inside the chart. Small pies on the left indicate apoptosis- and metabolism-related proteins of interest.</p
siRNA silencing of AK3 or DDX46 expression inhibits cell growth.
<p>(<b>A</b>) Differential expression of the 4 proteins not previously connected to any cancer between healthy and CLL individuals. (<b>B-D</b>) MEC-1 cells were transfected with (50 nM) scrambled siRNA (si-Scr,), one of the 2 different siRNAs against AK3 (siAK3 1 or 2), or against DDX46 (si-DDX46 1 or 2), a combination of siAK3 1 and 2 or a combination of siDDX46 1 and 2 and, at the indicated time, were analyzed for AK3 and DDX46 mRNA levels by RT-PCR (<b>B,C</b>) or analyzed for cell growth using the SRB method (n = 3) (<b>D</b>).</p
Comparison of apoptosis-related proteins in CLL patient- and healthy donor-derived PBMCs.
<p>Scatter plots display the expression levels of VDAC1 (<b>A</b>), MAVS (<b>B</b>), Bcl-2 (<b>C</b>), SMAC/Diablo (<b>D</b>), AIF (<b>E</b>), HK-I (<b>F</b>) and Bax (<b>G</b>), for each control subject and CLL patient, as analyzed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0148500#pone.0148500.g002" target="_blank">Fig 2</a>. Statistics were calculated with GraphPad Prism software. Horizontal lines represent mean values for each group. A difference between the healthy donor and CLL patient groups was considered statistically significant when P < 0.001 (***) or P < 0.01 (**), as determined by the Mann-Whitney test.</p
Over-expression of Bcl-2, VDAC, AIF, MAVS, SMAC/Diablo and PPWD1 in PBMCs from CLL patients.
<p>Immunoblot analysis of cell lysates of PBMCs derived from CLL patients (P) and healthy donors (H) probed with antibodies directed against VDAC1 [A<b>a</b>, n = 28 (P), 20 (H)], Bcl-2 [A<b>b</b>, n = 28 (P), 20 (H)], MAVS [A<b>c</b>, n = 28 (P), 19 (H)], SMAC/Diablo [A<b>d</b>, n = 21 (P), 15 (H)], AIF [Ae, n = 17 (P), 16 (H)], HK-I [A<b>f</b>, n = 28 (P), 20 (H)], BAX [A<b>g</b>, n = 6 (P), 6 (H)], PPWD1 [A<b>h</b>, n = 16(P), 10(H)] or β-actin. Representative immunoblots (<b>A</b>) and quantitative analysis (mean ± SEM) (<b>B</b>) of protein levels of healthy donors (white) and CLL patients (grey) of these and other samples are presented. For each sample, three independent immunoblots were performed. A difference between healthy and CLL groups was considered statistically significant when P < 0.001 (***) or P < 0.01 (**), as determined by the Mann-Whitney test.</p