Alberto Molano

• Albert Einstein College of Medicine

An investigation was carried out of the stage-specific effects of lithium and zinc on planaria embryologic development. These two reagents had dramatically different effects on the morphological development of planaria: Zinc induced the formation of bifurcations or trifurcations of the head region. In contrast, lithium induced the formation of roun...

An investigation was carried out of the stage-specific effects of barium, a wide spectrum potassium channel blocker that depolarizes cells, on planaria embryologic development. Barium exposure triggered a variety of axes abnormalities in planaria, including dorsoventral malformations (formation of pigmented dorsal bulges, suggestive of BMP up-regul...

Bioelectric signalling has been implicated in planaria regeneration and anatomical homeostasis. Previous reports demonstrated that barium chloride (1 mM), a potassium channel blocker, produced slow disintegration of the head (in 72 hours) in a clonal strain of Dugesia japonica. To investigate whether the effects of barium were similar in all planar...

This book is about the history of respiration. It differs slightly from previous ones because it places the electron at the center of the story. Very little has been written about this topic in the last 50 years. In the meantime, significant discoveries in the emerging field of quantum biology have shed new light on the central role of quantum mech...

To determine whether changes in sphingolipid composition are associated with age-related immune dysfunction, we analyzed the core sphingolipidome (i.e., all of the metabolites through the first headgroup additions) of young and aged CD4(+) T cells. Since sphingolipids influence the biophysical properties of membranes, we evaluated the compositions...

The increased sphingolipid abundances observed in aged CD4+ T cell non-IS fractions are largely independent of fatty acyl chain length. Individual subspecies amounts present in bead-depleted sonicates (non-IS fractions) prepared from equivalent numbers (20×106) of purified young and old murine CD4+ T cells. White bars indicate results for young CD4...

The increased sphingolipid abundances observed in aged CD4+ T cell IS fractions are largely independent of fatty acyl chain length. Individual subspecies amounts present in bead-enriched (IS) fractions prepared from equivalent numbers (20×106) of purified young and old murine CD4+ T cells. White bars indicate results for young CD4+ T cells. Gray ba...

CD4+T cells from aged humans or mice show significant reductions in IL-2 production upon activation. The resulting decreased proliferation is linked to higher risks of infection in the elderly. Several lines of evidence indicate that intrinsic defects preferentially affecting the naïve subset of CD4+T cells contribute to this reduced IL-2 productio...

CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating alpha galactosylceramide (alphaGalCer) analogs that give predominantly Th2 cell-type cytok...

The cytokine TWEAK demonstrates potent kidney proinflammatory and proliferative effects. Recently, we have shown that interactions of TWEAK with its receptor Fn14 are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host (cGVH) induced model of lupus. Fn14 is expressed by macrophages and resident kidney cells; we hypothesiz...

The intracellular enzyme indoleamine 2,3-dioxygenase (IDO), which degrades the rare and essential amino acid tryptophan and converts it into a series of biologically active catabolites, has been linked to the regulation of immune tolerance by specific dendritic cell subsets, and to the downmodulation of exacerbated immune responses. Although the im...

TNF-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily, is a prominent inducer of proinflammatory cytokines in vitro and in vivo. We previously found that kidney cells display the TWEAK receptor Fn14, and that TWEAK stimulation of mesangial cells and podocytes induces a potent proinflammatory response. Several of the cytokines...

Activation of CD1d-restricted invariant NKT (iNKT) cells by alpha-galactosylceramide (alphaGalCer) significantly suppresses development of diabetes in NOD mice. The mechanisms of this protective effect are complex, involving both Th1 and Th2 cytokines and a network of regulatory cells including tolerogenic dendritic cells. In the current study, we...

Accumulating evidence supports the notion that invariant NKT cells that recognize glycolipids presented by CD1d can play a role in the regulation of certain types of autoimmunity. Focusing mainly on studies of type 1 diabetes and several other common autoimmune diseases, we present an overview of the available knowledge and current speculations on...

CD1d-restricted NKT cells expressing invariant TCR alpha-chain rearrangements (iNKT cells) have been reported to be deficient in humans with a variety of autoimmune syndromes and in certain strains of autoimmune mice. In addition, injection of mice with alpha-galactosylceramide, a specific glycolipid agonist of iNKT cells, activates these T cells a...

A form of α-galactosylceramide, KRN7000, activates CD1d-restricted Vα14-invariant (Vα14i) natural killer (NK) T cells and initiates multiple downstream immune reactions. We report that substituting the C26:0 N-acyl chain of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of Vα14i NKT cell activation. One analogue containing a diu...

The mycobacterial cell wall component lipoarabinomannan (LAM) has been described as a virulence factor of Mycobacterium tuberculosis, and modification of the terminal arabinan residues of this compound with mannose caps (producing mannosyl-capped LAM [ManLAM]) in M. tuberculosis or with phosphoinositol caps (producing phosphoinositol-capped LAM [PI...

We immunized mice with an attenuated (cold-adapted) influenza virus followed by an attenuated vaccinia virus (modified vaccinia virus Ankara), both expressing a CD8+-T-cell epitope derived from malaria sporozoites. This vaccination regimen elicited high levels of protection against malaria. This is the first time that the vaccine efficacy of a reco...

Previously, we described H-2K(bW9) (K(bW9)), an engineered variant of the murine MHC class I molecule H-2K(b) (K(b)), devoid of the central anchor ("C") pocket owing to a point mutation on the floor of the peptide binding site; this substitution drastically altered selection of bound peptides, such that the peptide repertoires of K(b) and K(bW9) ar...

Biochemical analysis has suggested that self GPI anchors are the main natural ligand associated with mouse CD1d molecules. A recent study reported that Valpha14+ NK T cells responded to self as well as foreign (parasite-derived) GPIs in a CD1d-dependent manner. It further reported that the IgG response to the Plasmodium berghei malarial circumsporo...

The peptide-binding site of the murine MHC class I molecule H-2Kb contains a deep C pocket, that is critical for peptide binding, as it accepts the anchor phenylalanine or tyrosine residue located in the middle (position 5, P5F/Y) of H-2Kb binding peptides. H-2Kb predominantly binds octameric peptides. By both criteria, H-2Kb is unique among the kn...

Both superantigens (SAG) and many anti-TCR monoclonal antibodies (mAb) have specificity for the V beta region of the TCR encoded by TCRBV genes. For instance the bacterial SAG staphylococcal enterotoxin E (SEE), the retroviral SAG MTV-9 and the mAb OT145 each react with human T cells expressing BV6S7. This BV gene encodes two common alleles. We fou...

CTL combat intracellular pathogens by killing infected cells. The molecular targets of their attack are foreign peptides bound to self MHC encoded class I molecules. Immunization of mice with peptides containing CTL determinants was shown to elicit CD4-dependent CTL. Here, we have achieved in vivo CTL priming with naturally processed 8-10 amino aci...

In the first field trial with synthetic malaria vaccine SPf66 in a large population naturally exposed to malaria, 9957 persons > 1 year old and residing on the Colombian Pacific coast received three doses of the vaccine. To evaluate vaccine safety, clinical observations were made 30 min and 48 h after each immunization. There were no adverse reacti...

The KEK (Lysine-Glutamic acid-Lysine) motif is frequently found in the primary structure of certain malaria proteins involved in invasion, and plays an important role in the interaction of these proteins with the erythrocyte. This motif is contained in a peptide which forms part of the polymeric synthetic malaria vaccine SPf 66, currently undergoin...

In the search for strategies which might help in the elucidation of molecular mechanisms involved in the red blood cell (RBC) invasion by P. falciparum merozoites, and with the specific aim of establishing whether synthetic peptides derived from selected parasite proteins bind to human RBCs, 26 different peptides were chemically synthesized and rad...