14 research outputs found
Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype
Abstract The aim of the present study was to establish mitochondrial cholesterol trafficking 18 kDa translocator protein (TSPO) as a potential therapeutic target, capable of increasing macrophage cholesterol efflux to (apo)lipoprotein acceptors. Expression and activity of TSPO in human (THP-1) macrophages were manipulated genetically and by the use of selective TSPO ligands
Designing sequential transcription logic: a simple genetic circuit for conditional memory
The ability to learn and respond to recurrent events depends on the capacity
to remember transient biological signals received in the past. Moreover, it may
be desirable to remember or ignore these transient signals conditioned upon
other signals that are active at specific points in time or in unique
environments. Here, we propose a simple genetic circuit in bacteria that is
capable of conditionally memorizing a signal in the form of a transcription
factor concentration. The circuit behaves similarly to a "data latch" in an
electronic circuit, i.e. it reads and stores an input signal only when
conditioned to do so by a "read command". Our circuit is of the same size as
the well-known genetic toggle switch (an unconditional latch) which consists of
two mutually repressing genes, but is complemented with a "regulatory front
end" involving protein heterodimerization as a simple way to implement
conditional control. Deterministic and stochastic analysis of the circuit
dynamics indicate that an experimental implementation is feasible based on
well-characterized genes and proteins. It is not known, to which extent
molecular networks are able to conditionally store information in natural
contexts for bacteria. However, our results suggest that such sequential logic
elements may be readily implemented by cells through the combination of
existing protein-protein interactions and simple transcriptional regulation.Comment: 20 pages, 5 figures; supplementary material available upon request
from the author
Renal function in patients with anemia and severe chronic heart failure: effects of iron medications
Aim. To investigate the prevalence of anemia and renal dysfunction combination among patients with severe chronic heart failure (CHF), as well as the effects of intravenous (i/v) iron therapy.Material and methods. In total, 42 patients (mean age 69,3+1,2 years) with Functional Class III-IV stable CHF (NYHA classification) were examined. Glomerular filtration rate (GFR) was calculated based on creatinine concentration (MDRD formula). Anemia was diagnosed by WHO criteria: hemoglobin (Hb) level <130 g/1 in men and <120 g/1 in women. Eleven patients were administered Venofer for 24 weeks. At baseline and after the treatment course, 6-minute walk test (6mw) was performed.Results. Anemia was diagnosed in 17 (40,5%) patients, including 13 with iron deficiency. Chronic renal failure (CRF; GFR< 60 ml/min) was observed in 64,7 % of the participants. Clinical and laboratory parameters were compared in patients with cardiorenal syndrome (GFR<60 ml/min) with or without anemia. Significant negative correlation was observed between Hb and creatinine levels (p=-0,02), with positive correlation between hematocrit (Ht) and GFR levels (p=0,044). Intravenous iron therapy was associated with a significant increase in Hb (from 128,2+14,4 to 139,0+17,4 g/1; p=0,03), Ht (from 38,4+3,5 to 41,3+5,06; p=0,03), and physical stress tolerance (PST), according to 6mw test results.Conclusion. The combination of cardiac pathology, renal dysfunction and iron-deficient anemia was typical of patients with severe CHF. Iron therapy was associated with significant increase in Hb, Ht, and PST levels, without any severe adverse effects
P1334: THE IMPACT OF IMMUNOSUPPRESSION ON RECONSTITUTION OF CMV-SPECIFIC T CELLS AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
P1347: THE POTENTIAL INFLUENCE OF KILLER CELL IMMUNOGLOBULIN-LIKE RECEPTOR–LIGAND MISMATCH ON THE PROGNOSIS OF HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ACUTE LEUKEMIA PATIENTS
P1348: COMPARISON OF NATURAL KILLER CELL RECONSTITUTION AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION DEPENDING ON THE VARIANT OF T-CELL DEPLETION
Evidence for Multimerization of Neu Proteins Involved in Polysialic Acid Synthesis in Escherichia coli
A C-Terminal Region of Yersinia pestis YscD Binds the Outer Membrane Secretin YscCâ–żâ€
YscD is an essential component of the plasmid pCD1-encoded type III secretion system (T3SS) of Yersinia pestis. YscD has a single transmembrane (TM) domain that connects a small N-terminal cytoplasmic region (residues 1 to 121) to a larger periplasmic region (residues 143 to 419). Deletion analyses established that both the N-terminal cytoplasmic region and the C-terminal periplasmic region are required for YscD function. Smaller targeted deletions demonstrated that a predicted cytoplasmic forkhead-associated (FHA) domain is also required to assemble a functional T3SS; in contrast, a predicted periplasmic phospholipid binding (BON) domain and a putative periplasmic “ring-building motif” domain of YscD could be deleted with no significant effect on the T3S process. Although deletion of the putative “ring-building motif” domain did not disrupt T3S activity per se, the calcium-dependent regulation of the T3S apparatus was affected. The extreme C-terminal region of YscD (residues 354 to 419) was essential for secretion activity and had a strong dominant-negative effect on the T3S process when exported to the periplasm of the wild-type parent strain. Coimmunoprecipitation studies demonstrated that this region of YscD mediates the interaction of YscD with the outer membrane YscC secretin complex. Finally, replacement of the YscD TM domain with a TM domain of dissimilar sequence had no effect on the T3S process, indicating that the TM domain has no sequence-specific function in the assembly or function of the T3SS