Risk factors for failure of manipulation under anesthesia after total knee arthroplasty.

Background: Manipulation under anesthesia (MUA) is a well-established treatment for stiffness after total knee arthroplasty (TKA). Risk factors for failure of MUA remain largely unknown. The primary aim of this study was to identify risk factors for failure of MUA after TKA.

Measurement of Bradykinin Formation and Degradation in Blood Plasma: Relevance for Acquired Angioedema Associated With Angiotensin Converting Enzyme Inhibition and for Hereditary Angioedema Due to Factor XII or Plasminogen Gene Variants.

Bradykinin (BK)-mediated angioedema (AE) states are rare acquired or hereditary conditions involving localized edema of the subcutaneous and submucosal tissues. Citrated plasma from healthy volunteers or patients with hereditary angioedema (HAE) with normal level of C1-inhibitor (C1-INH) was used to investigate pathways of BK formation and breakdown relevant to AE physiopathology. The half-life of BK (100 nM) added to normal plasma was 34 s, a value that was increased ~12-fold when the angiotensin converting enzyme (ACE) inhibitor enalaprilat (130 nM) was added (enzyme immunoassay measurements).

FANCC localizes with UNC5A at neurite outgrowth and promotes neuritogenesis.

Objective: The Uncoordinated 5A (UNC5A) protein is part of a family of receptors that play roles in axonal pathfinding and cell migration. We previously showed that the Fanconi anemia C protein (FANCC) interacts with UNC5A and delays UNC5A-mediated apoptosis. FANCC is a predominantly cytoplasmic protein that has multiple functions including DNA damage signaling, oxygen radical metabolism, signal transduction, transcriptional regulation and apoptosis.

Fanconi anemia core complex-dependent HES1 mono-ubiquitination regulates its transcriptional activity.

Objective: The Hairy Enhancer of Split 1 (HES1) is a transcriptional repressor that regulates cellular proliferation and differentiation during development. We previously found an interaction between HES1 and Fanconi anemia (FA) proteins. FA is a hematological and developmental disorder caused by mutations in more than 20 different genes.

The Fanconi anemia group C protein interacts with uncoordinated 5A and delays apoptosis.

The Fanconi anemia group C protein (FANCC) is one of the several proteins that comprise the Fanconi anemia (FA) network involved in genomic surveillance. FANCC is mainly cytoplasmic and has many functions, including apoptosis suppression through caspase-mediated proteolytic processing. Here, we examined the role of FANCC proteolytic fragments by identifying their binding partners.

The Fanconi anemia pathway has a dual function in Dickkopf-1 transcriptional repression.

Fanconi anemia (FA) is an inherited bone marrow failure syndrome associated with a progressive decline in hematopoietic stem cells, developmental defects, and predisposition to cancer. These various phenotypic features imply a role of FA proteins in molecular events regulating cellular homeostasis. Interestingly, we previously found that the Fanconi C protein (FANCC) interacts with the C-terminal-binding protein-1 (CtBP1) involved in transcriptional regulation.

Fanconi anemia proteins interact with CtBP1 and modulate the expression of the Wnt antagonist Dickkopf-1.

Fanconi anemia (FA) is a genetic disorder characterized by congenital abnormalities, bone marrow failure, and increased susceptibility to cancer. Of the fifteen FA proteins, Fanconi anemia group C (FANCC) is one of eight FA core complex components of the FA pathway. Unlike other FA core complex proteins, FANCC is mainly localized in the cytoplasm, where it is thought to function in apoptosis, redox regulation, cytokine signaling, and other processes.

δ-Catenin is genetically and biologically associated with cortical cataract and future Alzheimer-related structural and functional brain changes.

Multiple lines of evidence suggest that specific subtypes of age-related cataract (ARC) and Alzheimer disease (AD) are related etiologically. To identify shared genetic factors for ARC and AD, we estimated co-heritability of quantitative measures of cataract subtypes with AD-related brain MRI traits among 1,249 members of the Framingham Eye Study who had a brain MRI scan approximately ten years after the eye exam. Cortical cataract (CC) was found to be co-heritable with future development of AD and with several MRI traits, especially temporal horn volume (THV, ρ = 0.

Hypothermia-induced hyperphosphorylation: a new model to study tau kinase inhibitors.

Tau hyperphosphorylation is one hallmark of Alzheimer's disease (AD) pathology. Pharmaceutical companies have thus developed kinase inhibitors aiming to reduce tau hyperphosphorylation. One obstacle in screening for tau kinase inhibitors is the low phosphorylation levels of AD-related phospho-epitopes in normal adult mice and cultured cells.

Silencing of amyloid precursor protein expression using a new engineered delta ribozyme.

Alzheimer's disease (AD) etiological studies suggest that an elevation in amyloid-β peptides (Aβ) level contributes to aggregations of the peptide and subsequent development of the disease. The major constituent of these amyloid peptides is the 1 to 40-42 residue peptide (Aβ(40-42)) derived from amyloid protein precursor (APP). Most likely, reducing Aβ levels in the brain may block both its aggregation and neurotoxicity and would be beneficial for patients with AD.

Identification of novel NPRAP/δ-catenin-interacting proteins and the direct association of NPRAP with dynamin 2.

Neural plakophilin-related armadillo protein (NPRAP or δ-catenin) is a neuronal-specific protein that is best known for its interaction with presenilin 1 (PS1). Interestingly, the hemizygous loss of NPRAP is associated with severe mental retardation in cri du chat syndrome (CDCS), and mutations in PS1 cause an aggressive, early-onset form of Alzheimer's disease. Until recently, studies on the function of NPRAP have focused on its ability to modulate dendritic protrusion elaboration through its binding to cell adhesion and scaffolding molecules.

A nuclear function for the presenilin 1 neuronal partner NPRAP/δ-catenin.

Presenilin-1 (PS1) is a broadly expressed transmembrane protein that is often mutated in familial Alzheimer's disease (AD). In addition to its role in amyloid production, PS1 interacts with several protein partners, including the neural plakophilin-related armadillo protein (NPRAP or δ-catenin). Although studies have suggested that NPRAP affects cell adhesion, other data suggest that it can modulate gene expression.

Cell membrane expression of cardiac sodium channel Na(v)1.5 is modulated by alpha-actinin-2 interaction.

Cardiac sodium channel Na(v)1.5 plays a critical role in heart excitability and conduction. The molecular mechanism that underlies the expression of Na(v)1.

The fanconi anemia core complex acts as a transcriptional co-regulator in hairy enhancer of split 1 signaling.

Mutations in one of the 13 Fanconi anemia (FA) genes cause a progressive bone marrow failure disorder associated with developmental abnormalities and a predisposition to cancer. Although FA has been defined as a DNA repair disease based on the hypersensitivity of patient cells to DNA cross-linking agents, FA patients develop various developmental defects such as skeletal abnormalities, microphthalmia, and endocrine abnormalities that may be linked to transcriptional defects. Recently, we reported that the FA core complex interacts with the transcriptional repressor Hairy Enhancer of Split 1 (HES1) suggesting that the core complex plays a role in transcription.

HES1 is a novel interactor of the Fanconi anemia core complex.

Fanconi anemia (FA) proteins are thought to play a role in chromosome stability and repair of DNA cross-links; however, these functions may not fully explain the developmental abnormalities and bone marrow failure that are characteristic of FA individuals. Here we associate the FA proteins with the Notch1 developmental pathway through a direct protein-protein interaction between the FA core complex and the hairy enhancer of split 1 (HES1). HES1 interaction with FA core complex members is dependent on a functional FA pathway.

Isolation of free-living dinitrogen-fixing bacteria and their activity in compost containing de-inking paper sludge.

Knowledge of the microbiology of dinitrogen (N2)-fixing bacteria in compost rich in de-inking paper sludge (DPS) is limited. Dinitrogen (N2)-fixing bacteria from DPS composts were isolated and studied for their N2-fixing activity in vitro and in vivo. Two Gram-negative N2-fixing isolates were identified as Pseudomonas.

Dissociated phenotypes in presenilin transgenic mice define functionally distinct gamma-secretases.

Gamma-secretase depends on presence of presenilins (PS), Nct, Aph-1, and PEN-2 within a core complex. This endoproteolytic activity cleaves within transmembrane domains of amyloid-beta precursor protein (APP) and Notch, and familial Alzheimer's disease (FAD) mutations in PS1 or PS2 genes shift APP cleavage from production of amyloid-beta (Abeta) 40 peptide to greater production of Abeta42. Although studies in PS1/PS2-deficient embryonic cells define overlapping activities for these proteins, in vivo complementation of PS1-deficient animals described here reveals an unexpected spectrum of activities dictated by PS1 and PS2 alleles.

Presence and active synthesis of the 67 kDa elastin-receptor in human circulating white blood cells.

Early after the identification of the elastin-receptor (El-R) on mesenchymal cells, it was demonstrated that phagocytic cells and lymphocytes could also respond to elastin peptides. Nevertheless, the level of El-R expression has never been demonstrated on immune cells and no data exist whether these cells actively synthesize this El-R. Thus, our aim in the present work was to study the expression and number of El-R on white blood cells (WBC) using a specific 67 kDa El-R antibody and to demonstrate the presence of mRNA corresponding to the gene coding for El-R.

Regulation of the Fanconi anemia group C protein through proteolytic modification.

The function of the Fanconi anemia group C protein (FANCC) is still unknown, though many studies point to a role in damage response signaling. Unlike other known FA proteins, FANCC is mainly localized to the cytoplasm and is thought to act as a messenger of cellular damage rather than an effector of repair. FANCC has been shown to interact with several cytoplasmic and nuclear proteins and to delay the onset of apoptosis through redox regulation of GSTP1.

Presenilin-1 is indirectly implicated in Notch1 cleavage.

It has been previously demonstrated that the Notch1 signalling pathway is impaired in presenilin-1 null cells. This observation suggests a role for presenilin-1 in the Notch1 developmental pathway, possibly through physical interaction. Here, we show that presenilin-1 and Notch1 do not interact directly with each other but are associated in the cell.

Oligomerization of human presenilin-1 fragments.

To gain insight into presenilin-1 (PS1) structural aspects, we explored the structure-function relationship of its N- and C-terminal (NTF and CTF, respectively) complexes. We demonstrated that both NTF and CTF act as independent but inter-changing binding units capable of binding each other (NTF/CTF) or their homologues (NTF/NTF; CTF/CTF). The Alzheimer's disease-associated PS1 mutations Y115H and M146L do not affect their ability to hetero- and/or homodimerize, thus conserving their basic integrity and function(s).

Presenilin-1 interacts directly with the beta-site amyloid protein precursor cleaving enzyme (BACE1).

A neuropathological hallmark of Alzheimer's disease is the presence of amyloid plaques. The major constituent of these plaques, occurring largely in brain areas important for memory and cognition, is the 40-42 amyloid residues (Abeta). Abeta is derived from the amyloid protein precursor after cleavage by the recently identified beta-secretase (BACE1) and the putative gamma-secretase complex containing presenilin 1 (PS1).

Dimerization of presenilin-1 in vivo: suggestion of novel regulatory mechanisms leading to higher order complexes.

A growing body of evidence indicates that presenilins could exist and be active as oligomeric complexes. Using yeast two-hybrid and cell culture analysis, we provide evidence that presenilin-1 (PS1) may self-oligomerize giving rise to specific full-length/full-length homodimers. When expressed in N2A and HEK239T cultured cells, full-length PS1-wt and 5(')myc-PS1-wt form specific homodimers corresponding to twice their molecular weight.